Gene expression patterns and susceptibility to allergic responses

References

• Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J. Allergy Clin. Immunol. 116, 377–383 (2005).
   PubMed Web of Science ®Google Scholar
• Sampson HA. Clinical practice. Peanut allergy. N. Engl. J. Med. 346, 1294–1299 (2002).
   PubMed Web of Science ®Google Scholar
• Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Ann. Rev. Immunol. 17, 255–281 (1999).
   PubMedGoogle Scholar
• Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Ann. Rev. Immunol. 22, 789–815 (2004).
   PubMed Web of Science ®Google Scholar
• Georas SN, Beck LA, Stellato C. What is eotaxin doing in the pleura? Insights into innate immunity from pleural mesothelial cells. Am. J. Respir. Cell Mol. Biol. 26, 384–387 (2002).
   PubMedGoogle Scholar
• Vercelli D. Genetic polymorphism in allergy and asthma. Curr. Opin. Immunol. 15, 609–613 (2003).
   PubMed Web of Science ®Google Scholar
• Hoffjan S, Nicolae D, Ober C. Association studies for asthma and atopic diseases: a comprehensive review of the literature. Respir. Res. 4, 14 (2003).
   PubMed Web of Science ®Google Scholar
• Eder W, von Mutius E. Hygiene hypothesis and endotoxin: what is the evidence? Curr. Opin. Allergy Clin. Immunol. 4, 113–117 (2004).
   PubMedGoogle Scholar
• Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N. Engl. J. Med. 343, 538–543 (2000).
   PubMed Web of Science ®Google Scholar
• Braun-Fahrlander C, Riedler J, Herz U et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl J. Med. 347, 869–877 (2002).
   PubMedGoogle Scholar
• Zutavern A, Hirsch T, Leupold W, Weiland S, Keil U, von Mutius E. Atopic dermatitis, extrinsic atopic dermatitis and the hygiene hypothesis: results from a cross-sectional study. Clin. Exp. Allergy 35, 1301–1308 (2005).
   PubMed Web of Science ®Google Scholar
• Celedon JC, Wright RJ, Litonjua AA et al. Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years. Am. J. Respir. Crit. Care Med. 167, 1239–1243 (2003).
   PubMed Web of Science ®Google Scholar
• Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev. Immunol. 1, 69–75 (2001).
   PubMedGoogle Scholar
• Holt PG, Thomas WR. Sensitization to airborne environmental allergens: unresolved issues. Nature Immunol. 6, 957–960 (2005).
   PubMed Web of Science ®Google Scholar
• Robinson D, Hamid Q, Ying S et al. Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-γ cytokine gene expression. Am. Rev. Respir. Dis. 148, 401–406 (1993).
   PubMed Web of Science ®Google Scholar
• Robinson D, Ying S, Bentley A et al. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J. Allergy Clin. Immunol. 92, 397–403 (1993).
   PubMed Web of Science ®Google Scholar
• Robinson DS, Hamid Q, Ying S et al. Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl J. Med. 326, 298–304 (1992).
   PubMed Web of Science ®Google Scholar
• Leung DY, Martin RJ, Szefler SJ et al. Dysregulation of interleukin-4, interleukin-5, and interferon gamma gene expression in steroid-resistant asthma. J. Exp. Med. 181, 33–40 (1995).
   PubMed Web of Science ®Google Scholar
• Benson M, Strannegard IL, Wennergren G, Strannegard O. Low levels of interferon-γ in nasal fluid accompany raised levels of T-helper 2 cytokines in children with ongoing allergic rhinitis. Pediatr. Allergy Immunol. 11, 20–28 (2000).
   PubMed Web of Science ®Google Scholar
• Lee CH, Rhee CS, Oh SH, Min YG, Lee MS. Increase in expression of IL-4 and IL-5 mRNA in the nasal mucosa of patients with perennial allergic rhinitis during natural allergen exposure. Ann. Otol. Rhinol. Laryngol. 106, 215–219 (1997).
   PubMedGoogle Scholar
• Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J. Clin. Invest. 94, 870–876 (1994).
   PubMed Web of Science ®Google Scholar
• Martin RJ, Boguniewicz M, Henson JE et al. The effects of inhaled interferon gamma in normal human airways. Am. Rev. Respir. Dis. 148, 1677–1682 (1993).
   PubMedGoogle Scholar
• Randolph DA, Stephens R, Carruthers CJ, Chaplin DD. Co-operation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Invest. 104, 1021–1029 (1999).
   PubMed Web of Science ®Google Scholar
• Ford JG, Rennick D, Donaldson DD et al. Il-13 and IFN-γ: interactions in lung inflammation. J. Immunol. 167, 1769–1777 (2001).
   PubMedGoogle Scholar
• Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon γ regulate allergic airway inflammation and mucus production. J. Exp. Med. 190, 1309–1318 (1999).
   PubMed Web of Science ®Google Scholar
• Magnan AO, Mely LG, Camilla CA et al. Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFN-γ-producing CD8+ T cells in asthma. Am. J. Respir. Crit. Care Med. 161, 1790–1796 (2000).
   PubMed Web of Science ®Google Scholar
• Heaton T, Rowe J, Turner S et al. An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet 365, 142–149 (2005).
   PubMed Web of Science ®Google Scholar
• Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J. Clin. Invest. 113, 651–657 (2004).
   PubMed Web of Science ®Google Scholar
• Thepen T, Langeveld-Wildschut EG, Bihari IC et al. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial Th2 response to a Th1 response in situ: an immunocytochemical study. J. Allergy Clin. Immunol. 97, 828–837 (1996).
   PubMed Web of Science ®Google Scholar
• Ingordo V, Dalle Nogare R, Colecchia B, D’Andria C. Is the atopy patch test with house dust mites specific for atopic dermatitis? Dermatology 209, 276–283 (2004).
   PubMedGoogle Scholar
• Wollenberg A, Kraft S, Hanau D, Bieber T. Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J. Invest. Dermatol. 106, 446–453 (1996).
   PubMed Web of Science ®Google Scholar
• Novak N, Valenta R, Bohle B et al. FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J. Allergy Clin. Immunol. 113, 949–957 (2004).
   PubMedGoogle Scholar
• de Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, Bihari IC, Bruijnzeel-Koomen CA, Thepen T. Nonspecific T-cell homing during inflammation in atopic dermatitis: expression of cutaneous lymphocyte-associated antigen and integrin αE β7 on skin-infiltrating T cells. J. Allergy Clin. Immunol. 100, 694–701 (1997).
   PubMed Web of Science ®Google Scholar
• Wu C, Fargeas C, Nakajima T, Delespesse G. Glucocorticoids suppress the production of interleukin-4 by human lymphocytes. Eur. J. Immunol. 21, 2645–2647 (1991).
   PubMed Web of Science ®Google Scholar
• Byron K, Varigo G, Wootton A. Hydrocortisone inhibition of human interleukin-4. Immunol. 77, 624–626 (1992).
   PubMedGoogle Scholar
• Chikanza LC, Panayi GS. The effects of hydrocortisone on in vitro lymphocyte proliferation and interleukin-2 and -4 production in corticosteroid sensitive and resistant subjects. Eur. J. Clin. Invest. 23, 845–850 (1993).
   PubMed Web of Science ®Google Scholar
• Schmidt J, Fleissner S, Heimann-Weitschat I, Lindstaedt R, Szelenyi I. The effect of different corticosteroids and cyclosporin A on interleukin-4 and interleukin-5 release from murine Th2-type T cells. Eur. J. Pharmacol. 260, 247–250 (1994).
   PubMed Web of Science ®Google Scholar
• Krouwels F, van der Heijden J, Lutter R, van Neervan R, Jansen H, Out T. Glucocorticoids affect functions of airway and blood-derived human T cell clones. Am. J. Respir. Cell Mol. Biol. 14, 388–397 (1996).
   PubMedGoogle Scholar
• Umland SP, Nahrebne DK, Razac S et al. The inhibitory effects of topically active glucocorticoids on IL-4, IL-5, and interferon-γ production by cultured primary CD4+ T cells. J. Allergy Clin. Immunol. 100, 511–519 (1997).
   PubMed Web of Science ®Google Scholar
• Braun CM, Huang SK, Bashian GG, Kagey-Sobotka A, Lichtenstein LM, Essayan DM. Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses. J. Allergy Clin. Immunol. 100, 400–407 (1997).
   PubMed Web of Science ®Google Scholar
• Naseer T, Minshall EM, Leung DY et al. Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am. J. Respir. Crit. Care Med. 155, 845–851 (1997).
   PubMed Web of Science ®Google Scholar
• Corrigan CJ, Hamid Q, North J et al. Peripheral blood CD4 but not CD8 t-lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-Type pattern: effect of glucocorticoid therapy. Am. J. Respir. Cell Mol. Biol. 12, 567–578 (1995).
   PubMed Web of Science ®Google Scholar
• Majori M, Piccoli ML, Bertacco S, Cuomo A, Cantini L, Pesci A. Inhaled beclomethasone dipropionate downregulates CD4 and CD8 T-lymphocyte activation in peripheral blood of patients with asthma. J. Allergy Clin. Immunol. 100, 379–382 (1997).
   PubMedGoogle Scholar
• Gemou-Engesaeth V, Bush A, Kay AB, Hamid Q, Corrigan CJ. Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and ‘Th2-type’ cytokine mRNA expression. Pediatrics 99, 695–703 (1997).
   PubMedGoogle Scholar
• Gemou-Engesaeth V, Fagerhol MK, Toda M et al. Expression of activation markers and cytokine mRNA by peripheral blood CD4 and CD8 T cells in atopic and nonatopic childhood asthma: effect of inhaled glucocorticoid therapy. Pediatrics 109, E24 (2002).
   Google Scholar
• Harris NL, Watt V, Ronchese F, Le Gros G. Differential T cell function and fate in lymph node and nonlymphoid tissues. J. Exp. Med. 195, 317–326 (2002).
   PubMed Web of Science ®Google Scholar
• Reinhardt RL, Bullard DC, Weaver CT, Jenkins MK. Preferential accumulation of antigen-specific effector CD4 T cells at an antigen injection site involves CD62E-dependent migration but not local proliferation. J. Exp. Med. 197, 751–762 (2003).
   PubMedGoogle Scholar
• Seki N, Miyazaki M, Suzuki W et al. IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation. J. Immunol. 172, 6158–6166 (2004).
   PubMedGoogle Scholar
• Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nature Rev. Immunol. 2, 933–944 (2002).
   PubMed Web of Science ®Google Scholar
• Grogan JL, Mohrs M, Harmon B, Lacy DA, Sedat JW, Locksley RM. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14, 205–215 (2001).
   PubMed Web of Science ®Google Scholar
• Eisenbarth SC, Zhadkevich A, Ranney P, Herrick CA, Bottomly K. IL-4-dependent Th2 collateral priming to inhaled antigens independent of toll-like receptor 4 and myeloid differentiation factor 88. J. Immunol. 172, 4527–4534 (2004).
   PubMed Web of Science ®Google Scholar
• Usui T, Nishikomori R, Kitani A, Strober W. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rβ2 chain or T-bet. Immunity 18, 415–428 (2003).
   PubMed Web of Science ®Google Scholar
• Galvao Da Silva AP, Jacysyn JF, De Almeida Abrahamsohn I. Resistant mice lacking interleukin-12 become susceptible to Trypanosoma cruzi infection but fail to mount a T helper Type 2 response. Immunology 108, 230–237 (2003).
   PubMedGoogle Scholar
• Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell Type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645–1651 (2002).
   PubMed Web of Science ®Google Scholar
• Groux H, O’Garra A, Bigler M et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997).
   PubMed Web of Science ®Google Scholar
• Richards DF, Fernandez M, Caulfield J, Hawrylowicz CM. Glucocorticoids drive human CD8+ T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production. Eur. J. Immunol. 30, 2344–2354 (2000).
   PubMed Web of Science ®Google Scholar
• Barrat FJ, Cua DJ, Boonstra A et al. In vitro generation of interleukin-10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper Type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med. 195, 603–616 (2002).
   PubMed Web of Science ®Google Scholar
• Vieira PL, Christensen JR, Minaee S et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 172, 5986–5993 (2004).
   PubMed Web of Science ®Google Scholar
• O’Garra A, Barrat FJ. In vitro generation of IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by Th1- and Th2-inducing cytokines. Immunol. Lett. 85, 135–139 (2003).
   PubMedGoogle Scholar
• Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421, 388–392 (2003).
   PubMed Web of Science ®Google Scholar
• Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Ann. Rev. Immunol. 19, 683–765 (2001).
   PubMed Web of Science ®Google Scholar
• Sakaguchi S. Naturally Arising CD4+ Regulatory T cells for immunologic self-tolerance and negative control of immune responses. Ann. Rev. Immunol. 22, 531–562 (2004).
   PubMed Web of Science ®Google Scholar
• Weiner HL. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol. Rev. 182, 207–214 (2001).
   PubMed Web of Science ®Google Scholar
• Bennett CL, Christie J, Ramsdell F et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genet. 27, 20–21 (2001).
   PubMed Web of Science ®Google Scholar
• Schubert LA, Jeffery E, Zhang Y, Ramsdell F, Ziegler SF. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 276, 37672–37679 (2001).
   PubMed Web of Science ®Google Scholar
• Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol. 4, 330–336 (2003).
   PubMed Web of Science ®Google Scholar
• Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003).
   PubMed Web of Science ®Google Scholar
• Kasprowicz DJ, Smallwood PS, Tyznik AJ, Ziegler SF. Scurfin (FoxP3) controls T-dependent immune responses in vivo through regulation of CD4+ T cell effector function. J. Immunol. 171, 1216–1223 (2003).
   PubMed Web of Science ®Google Scholar
• Watanabe N, Wang YH, Lee HK, Ito T, Cao W, Liu YJ. Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436, 1181–1185 (2005).
   PubMed Web of Science ®Google Scholar
• Walker MR, Kasprowicz DJ, Gersuk VH et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 112, 1437–1443 (2003).
   PubMed Web of Science ®Google Scholar
• Lin W, Truong N, Grossman WJ et al. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J. Allergy Clin. Immunol. 116, 1106–1115 (2005).
   PubMed Web of Science ®Google Scholar
• Ochs HD, Ziegler SF, Torgerson TR. Foxp3 acts as a rheostat of the immune response. Immunol. Rev. 203, 156–164 (2005).
   PubMed Web of Science ®Google Scholar
• Turcanu V, Maleki SJ, Lack G. Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J. Clin. Invest. 111, 1065–1072 (2003).
   PubMed Web of Science ®Google Scholar
• Umetsu DT, Akbari O, Dekruyff RH. Regulatory T cells control the development of allergic disease and asthma. J. Allergy Clin. Immunol. 112, 480–487; quiz 488 (2003).
   PubMed Web of Science ®Google Scholar
• Romagnani S. Immunologic influences on allergy and the Th1/Th2 balance. J. Allergy Clin. Immunol. 113, 395–400 (2004).
   PubMed Web of Science ®Google Scholar
• Robinson DS, Larche M, Durham SR. Tregs and allergic disease. J. Clin. Invest. 114, 1389–1397 (2004).
   PubMed Web of Science ®Google Scholar
• Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nature Immunol. 2, 725–731 (2001).
   PubMed Web of Science ®Google Scholar
• Hadeiba H, Locksley RM. Lung CD25 CD4 regulatory T cells suppress Type 2 immune responses but not bronchial hyper-reactivity. J. Immunol. 170, 5502–5510 (2003).
   PubMed Web of Science ®Google Scholar
• Zuany-Amorim C, Sawicka E, Manlius C et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nature Med. 8, 625–629 (2002).
   PubMedGoogle Scholar
• Chen W, Jin W, Hardegen N et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 198, 1875–1886 (2003).
   PubMed Web of Science ®Google Scholar
• Ling EM, Smith T, Nguyen XD et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363, 608–615 (2004).
   PubMed Web of Science ®Google Scholar
• Li-Weber M, Davydov I, Krafft H, Krammer P. The role of NF-Y and IRF-2 in the regulation of human IL-4 gene expression. J. Immunol. 153, 4122–4133 (1994).
   PubMedGoogle Scholar
• Lee RL, Fields PE, Flavell RA. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447–459 (2001).
   PubMed Web of Science ®Google Scholar
• Tykocinski LO, Hajkova P, Chang HD et al. A critical control element for interleukin-4 memory expression in T helper lymphocytes. J. Biol. Chem. 280, 28177–28185 (2005).
   PubMedGoogle Scholar
• Zhang DH, Cohn L, Ray P, Bottomly K, Ray A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272, 21597–21603 (1997).
   PubMed Web of Science ®Google Scholar
• Kaplan MH, Schindler U, Smiley ST, Grusby MJ. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4, 313–319 (1996).
   PubMed Web of Science ®Google Scholar
• Peng SL, Gerth AJ, Ranger AM, Glimcher LH. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity 14, 13–20 (2001).
   PubMed Web of Science ®Google Scholar
• Ho AM, Jain J, Rao A, Hogan PG. Expression of the transcription factor NFATp in a neuronal cell line and in the murine nervous system. J. Biol. Chem. 269, 28181–28186 (1994).
   PubMedGoogle Scholar
• Li B, Tournier C, Davis RJ, Flavell RA. Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation. Embo. J. 18, 420–432 (1999).
   PubMed Web of Science ®Google Scholar
• Fowell DJ, Shinkai K, Liao XC et al. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells. Immunity 11, 399–409 (1999).
   PubMed Web of Science ®Google Scholar
• Marsland BJ, Soos TJ, Spath G, Littman DR, Kopf M. Protein kinase C τ is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. J. Exp. Med. 200, 181–189 (2004).
   PubMed Web of Science ®Google Scholar
• Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J. Clin. Invest. 104, 985–993 (1999).
   PubMed Web of Science ®Google Scholar
• Ting CN, Olson MC, Barton KP, Leiden JM. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384, 474–478 (1996).
   PubMed Web of Science ®Google Scholar
• Zhu J, Min B, Hu-Li J et al. Conditional deletion of Gata3 shows its essential function in Th1-Th2 responses. Nature Immunol. 5, 1157–1165 (2004).
   PubMed Web of Science ®Google Scholar
• Yamashita M, Ukai-Tadenuma M, Kimura M et al. Identification of a conserved GATA3 response element upstream proximal of the IL-13 gene locus. J. Biol. Chem. 29, 29 (2002).
   Google Scholar
• Yamashita M, Ukai-Tadenuma M, Miyamoto T et al. Essential role of GATA3 for the maintenance of Th2 cytokine production and chromatin remodeling at the Th2 cytokine gene loci. J. Biol. Chem. 279(26), 26983–26990 (2004).
   PubMedGoogle Scholar
• Zhang DH, Yang L, Cohn L et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11, 473–482 (1999).
   PubMed Web of Science ®Google Scholar
• Nakamura Y, Ghaffar O, Olivenstein R et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J. Allergy Clin. Immunol. 103, 215–222 (1999).
   PubMed Web of Science ®Google Scholar
• Nakamura Y, Christodoulopoulos P, Cameron L et al. Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge. J. Allergy Clin. Immunol. 105, 1146–1152 (2000).
   PubMed Web of Science ®Google Scholar
• Arakawa S, Hatano Y, Katagiri K. Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis. Clin. Exp. Immunol. 135, 505–510 (2004).
   PubMedGoogle Scholar
• Caramori G, Lim S, Ito K et al. Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies. Eur. Respir. J. 18, 466–473 (2001).
   PubMed Web of Science ®Google Scholar
• Pykalainen M, Kinos R, Valkonen S et al. Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. J. Allergy Clin. Immunol. 115, 80–87 (2005).
   PubMed Web of Science ®Google Scholar
• Georas S, Cumberland J, Burke T, Chen R, Schindler U, Casolaro V. Stat6 inhibits interleukin-4 promoter activity in T cells. Blood 92, 4529–4538 (1998).
   PubMedGoogle Scholar
• Dorado B, Jerez MJ, Flores N, Martin-Saavedra FM, Duran C, Ballester S. Autocrine IL-4 gene regulation at late phases of TCR activation in differentiated Th2 cells. J. Immunol. 169, 3030–3037 (2002).
   PubMedGoogle Scholar
• Lee DU, Rao A. Molecular analysis of a locus control region in the T helper 2 cytokine gene cluster: a target for STAT6 but not GATA3. Proc. Natl Acad. Sci. USA 101, 16010–16015 (2004).
   PubMedGoogle Scholar
• Zhu J, Guo L, Min B et al. Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16, 733–744 (2002).
   PubMed Web of Science ®Google Scholar
• Kurata H, Lee HJ, O’Garra A, Arai N. Ectopic expression of activated Stat6 induces the expression of Th2- specific cytokines and transcription factors in developing Th1 cells. Immunity 11, 677–688 (1999).
   PubMed Web of Science ®Google Scholar
• Kuperman D, Schofield B, Wills-Karp M, Grusby MJ. Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production. J. Exp. Med. 187, 939–948 (1998).
   PubMed Web of Science ®Google Scholar
• Yagi R, Nagai H, Iigo Y, Akimoto T, Arai T, Kubo M. Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice. J. Immunol. 168, 2020–2027 (2002).
   PubMed Web of Science ®Google Scholar
• Christodoulopoulos P, Cameron L, Nakamura Y et al. Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J. Allergy Clin. Immunol. 107, 586–591 (2001).
   PubMedGoogle Scholar
• Ghaffar O, Christodoulopoulos P, Lamkhioued B et al. In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids. Clin. Exp. Allergy 30, 86–93 (2000).
   PubMedGoogle Scholar
• Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP. Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. Clin. Exp. Allergy 34, 1690–1700 (2004).
   PubMedGoogle Scholar
• Tamura K, Arakawa H, Suzuki M et al. Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases. Clin. Exp. Allergy 31, 1509–1514 (2001).
   PubMedGoogle Scholar
• Duetsch G, Illig T, Loesgen S et al. STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study. Hum. Mol. Genet. 11, 613–621 (2002).
   PubMed Web of Science ®Google Scholar
• Macian F. NFAT proteins: key regulators of T-cell development and function. Nature Rev. Immunol. 5, 472–484 (2005).
   PubMed Web of Science ®Google Scholar
• Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17, 2205–2232 (2003).
   PubMed Web of Science ®Google Scholar
• Crabtree GR. Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NFAT. Cell 96, 611–614 (1999).
   PubMed Web of Science ®Google Scholar
• Seminario CS, Burke T, Bochner B, Georas S. Detection of an NFAT-like protein in human eosinophils. Am. J. Respir. Crit. Care Med. 155, A58 (1997).
   Google Scholar
• Reddy SP, Mossman BT. Role and regulation of activator protein-1 in toxicant-induced responses of the lung. Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1161–L1178 (2002).
   PubMed Web of Science ®Google Scholar
• Ogawa K, Kaminuma O, Okudaira H et al. Transcriptional regulation of the IL-5 gene in peripheral T cells of asthmatic patients. Clin. Exp. Immunol. 130, 475–483 (2002).
   PubMed Web of Science ®Google Scholar
• Ho IC, Hodge MR, Rooney JW, Glimcher LH. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973–983 (1996).
   PubMed Web of Science ®Google Scholar
• Ho IC, Lo D, Glimcher LH. c-maf promotes T helper cell Type 2 (Th2) and attenuates Th1 differentiation by both interleukin-4-dependent and -independent mechanisms. J. Exp. Med. 188, 1859–1866 (1998).
   PubMed Web of Science ®Google Scholar
• Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH. NF-AT-Driven interleukin-4 transcription potentiated by NIP45. Science 274, 1903–1905 (1996).
   PubMedGoogle Scholar
• Kim JI, Ho IC, Grusby MJ, Glimcher LH. The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 10, 745–751 (1999).
   PubMed Web of Science ®Google Scholar
• Cousins DJ, Lee TH, Staynov DZ. Cytokine coexpression during human Th1/Th2 cell differentiation: direct evidence for co-ordinated expression of Th2 cytokines. J. Immunol. 169, 2498–2506 (2002).
   PubMed Web of Science ®Google Scholar
• Li-Weber M, Salgame P, Hu C et al. Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter. J. Immunol. 161, 1380–1389 (1998).
   PubMedGoogle Scholar
• Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nature Immunol. 4, 616–623 (2003).
   PubMed Web of Science ®Google Scholar
• Agarwal S, Rao A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765–775 (1998).
   PubMed Web of Science ®Google Scholar
• Solymar DC, Agarwal S, Bassing CH, Alt FW, Rao A. A 3’ enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells. Immunity 17, 41–50 (2002).
   PubMedGoogle Scholar
• Wang Y, Fischle W, Cheung W, Jacobs S, Khorasanizadeh S, Allis CD. Beyond the double helix: writing and reading the histone code. Novartis Found Symp. 259, 3–17; discussion 17–21, 163–169 (2004).
   PubMedGoogle Scholar
• Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).
   PubMed Web of Science ®Google Scholar
• Valapour M, Guo J, Schroeder JT et al. Histone deacetylation inhibits IL4 gene expression in T cells. J. Allergy Clin. Immunol. 109, 238–245 (2002).
   PubMedGoogle Scholar
• Fields PE, Kim ST, Flavell RA. Cutting edge: changes in histone acetylation at the IL-4 and IFN-γ loci accompany Th1/Th2 differentiation. J. Immunol. 169, 647–650 (2002).
   PubMed Web of Science ®Google Scholar
• Makar KW, Perez-Melgosa M, Shnyreva M, Weaver WM, Fitzpatrick DR, Wilson CB. Active recruitment of DNA methyltransferases regulates interleukin-4 in thymocytes and T cells. Nature Immunol. 4, 1183–1190 (2003).
   PubMedGoogle Scholar
• Santangelo S, Cousins DJ, Winkelmann NE, Staynov DZ. DNA methylation changes at human Th2 cytokine genes coincide with DNase I hypersensitive site formation during CD4+ T cell differentiation. J. Immunol. 169, 1893–1903 (2002).
   PubMed Web of Science ®Google Scholar
• Lee DU, Agarwal S, Rao A. Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16, 649–660 (2002).
   PubMed Web of Science ®Google Scholar
• Ansel KM, Greenwald RJ, Agarwal S et al. Deletion of a conserved IL-4 silencer impairs T helper Type 1-mediated immunity. Nature Immunol. 5, 1251–1259 (2004).
   PubMedGoogle Scholar
• Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655–669 (2000).
   PubMed Web of Science ®Google Scholar
• Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. Distinct effects of T-bet in Th1 lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science 295, 338–342 (2002).
   PubMed Web of Science ®Google Scholar
• Afkarian M, Sedy JR, Yang J et al. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nature Immunol. 3, 549–557 (2002).
   PubMed Web of Science ®Google Scholar
• Mullen AC, High FA, Hutchins AS et al. Role of T-bet in commitment of Th1 cells before IL-12-dependent selection. Science 292, 1907–1910 (2001).
   PubMed Web of Science ®Google Scholar
• Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307, 430–433 (2005).
   PubMed Web of Science ®Google Scholar
• Finotto S, De Sanctis GT, Lehr HA et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J. Exp. Med. 193, 1247–1260 (2001).
   PubMed Web of Science ®Google Scholar
• Breuer K, Wittmann M, Kempe K et al. Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper Type 1 response in atopic dermatitis. Clin. Exp. Allergy 35, 1088–1095 (2005).
   PubMed Web of Science ®Google Scholar
• Tantisira KG, Hwang ES, Raby BA et al. TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc. Natl Acad. Sci. USA 101, 18099–18104 (2004).
   PubMed Web of Science ®Google Scholar
• Raby BA, Hwang ES, Van Steen K et al. T-bet polymorphisms are associated with asthma and airway hyperresponsiveness. Am. J. Respir. Crit. Care Med.173(1), 64–70 (2006).
   PubMedGoogle Scholar
• Lambrecht BN, Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nature Rev. Immunol. 3, 994–1003 (2003).
   PubMed Web of Science ®Google Scholar
• Vermaelen K, Pauwels R. Pulmonary dendritic cells. Am. J. Respir. Crit. Care Med. 172, 530–551 (2005).
   PubMed Web of Science ®Google Scholar
• Holt PG, Haining S, Nelson DJ, Sedgwick JD. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol. 153, 256–261 (1994).
   PubMed Web of Science ®Google Scholar
• McWilliam AS, Nelson D, Thomas JA, Holt PG. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J. Exp. Med. 179, 1331–1336 (1994).
   PubMedGoogle Scholar
• Hawiger D, Inaba K, Dorsett Y et al. Dendritic cells induce peripheral T cell unresponsiveness under steady-state conditions in vivo. J. Exp. Med. 194, 769–779 (2001).
   PubMed Web of Science ®Google Scholar
• Steinman RM, Nussenzweig MC. Inaugural article: avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA 99, 351–358 (2002).
   PubMed Web of Science ®Google Scholar
• Takeda K, Kaisho T, Akira S. Toll-like receptors. Ann. Rev. Immunol. 21, 335–376 (2003).
   PubMed Web of Science ®Google Scholar
• Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430, 257–263 (2004).
   PubMed Web of Science ®Google Scholar
• Caux C, Massacrier C, Vanbervliet B et al. Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 180, 1263–1272 (1994).
   PubMed Web of Science ®Google Scholar
• Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184, 747–752 (1996).
   PubMed Web of Science ®Google Scholar
• MacDonald AS, Straw AD, Dalton NM, Pearce EJ. Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J. Immunol. 168, 537–540 (2002).
   PubMed Web of Science ®Google Scholar
• Rissoan MC, Soumelis V, Kadowaki N et al. Reciprocal control of T helper cell and dendritic cell differentiation [see comments]. Science 283, 1183–1186 (1999).
   PubMed Web of Science ®Google Scholar
• Turley SJ, Inaba K, Garrett WS et al. Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288, 522–527 (2000).
   PubMed Web of Science ®Google Scholar
• Caux C, Vanbervliet B, Massacrier C et al. B70/B7–2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J. Exp. Med. 180, 1841–1847 (1994).
   PubMed Web of Science ®Google Scholar
• Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of Th1, Th2 and nonpolarized T cells. Nature Immunol. 1, 311–316 (2000).
   PubMed Web of Science ®Google Scholar
• Ebner S, Ratzinger G, Krosbacher B et al. Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4. J. Immunol. 166, 633–641 (2001).
   PubMed Web of Science ®Google Scholar
• Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299, 1033–1036 (2003).
   PubMed Web of Science ®Google Scholar
• Lanzavecchia A, Sallusto F. Antigen decoding by T lymphocytes: from synapses to fate determination. Nature Immunol. 2, 487–492 (2001).
   PubMedGoogle Scholar
• Lanzavecchia A, Sallusto F. The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr. Opin. Immunol. 13, 291–298 (2001).
   PubMed Web of Science ®Google Scholar
• Huang Q, Liu D, Majewski P et al. The plasticity of dendritic cell responses to pathogens and their components. Science 294, 870–875 (2001).
   PubMed Web of Science ®Google Scholar
• Ronnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J. Exp. Med. 194, F59–F63 (2001).
   PubMed Web of Science ®Google Scholar
• Gilliet M, Boonstra A, Paturel C et al. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195, 953–958 (2002).
   PubMed Web of Science ®Google Scholar
• Blomberg S, Eloranta ML, Magnusson M, Alm GV, Ronnblom L. Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus. Arthritis Rheum. 48, 2524–2532 (2003).
   PubMed Web of Science ®Google Scholar
• Diebold SS, Montoya M, Unger H et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424, 324–328 (2003).
   PubMed Web of Science ®Google Scholar
• Asselin-Paturel C, Boonstra A, Dalod M et al. Mouse Type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nature Immunol. 2, 1144–1150 (2001).
   PubMedGoogle Scholar
• Ronnblom L, Eloranta ML, Alm GV. Role of natural interferon-alpha producing cells (plasmacytoid dendritic cells) in autoimmunity. AutoImmunity 36, 463–472 (2003).
   Google Scholar
• Boonstra A, Asselin-Paturel C, Gilliet M et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper Type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J. Exp. Med. 197, 101–109 (2003).
   PubMed Web of Science ®Google Scholar
• Charbonnier AS, Hammad H, Gosset P et al. Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response. J. Leukoc. Biol. 73, 91–99 (2003).
   PubMed Web of Science ®Google Scholar
• Kuipers H, Hijdra D, De Vries VC et al. Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells. J. Immunol. 171, 3645–3654 (2003).
   PubMed Web of Science ®Google Scholar
• Redecke V, Hacker H, Datta SK et al. Cutting edge: activation of toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J. Immunol. 172, 2739–2743 (2004).
   PubMed Web of Science ®Google Scholar
• Traidl-Hoffmann C, Mariani V, Hochrein H et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper Type 2 cell polarization. J. Exp. Med. 201, 627–636 (2005).
   PubMedGoogle Scholar
• Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote Type 2 cytokine production in maturing human naive T helper cells. J. Immunol. 159, 28–35 (1997).
   PubMed Web of Science ®Google Scholar
• Boldogh I, Bacsi A, Choudhury BK et al. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J. Clin. Invest. 115, 2169–2179 (2005).
   PubMed Web of Science ®Google Scholar
• Ranganath S, Murphy KM. Structure and specificity of GATA proteins in Th2 development. Mol. Cell Biol. 21, 2716–2725 (2001).
   PubMedGoogle Scholar