Key Regulators of Sensitization and Tolerance: GM-CSF, IL-10, TGF-β and the Notch Signaling Pathway in Adjuvant-Free Experimental Models of Respiratory Allergy

REFERENCES

• Cates EC, Gajewska BU, Goncharova S, Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization. J Allergy Clin Immunol 2003;111:1076–1086.
   PubMed Web of Science ®Google Scholar
• Okano M, Nishizaki K, Abe M, Strain-dependent induction of allergic rhinitis without adjuvant in mice. Allergy 1999;54:593–601.
   PubMedGoogle Scholar
• Renz H, Smith HR, Henson JE, Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol 1992;89:1127–1138.
   PubMed Web of Science ®Google Scholar
• Guibas GV, Makris M, Spandou E, Priftis KN. Exposure of immunologically naive laboratory rodents to antigen via the airways. Where does tolerance stop and sensitization begin? Clin Exp Allergy 2012;42:1552–1565.
   PubMed Web of Science ®Google Scholar
• Tournoy KG, Provoost S, Van Hove C, Joos G. The role of immune tolerance in asthma pathogenesis. Curr Allergy Asthma Rep 2006;6:437–443.
   PubMedGoogle Scholar
• Stampfli MR, Wiley RE, Neigh GS, GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice. J Clin Invest 1998;102:1704–1714.
   PubMed Web of Science ®Google Scholar
• Ritz SA, Stampfli MR, Davies DE, On the generation of allergic airway diseases: from GM-CSF to Kyoto. Trends Immunol 2002;23:396–402.
   PubMed Web of Science ®Google Scholar
• Cates EC, Fattouh R, Johnson JR, Modeling responses to respiratory house dust mite exposure. Contrib Microbiol 2007;14:42–67.
   PubMedGoogle Scholar
• Cates EC, Fattouh R, Wattie J, Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. J Immunol 2004;173:6384–6392.
   PubMed Web of Science ®Google Scholar
• Borchers MT, Justice PJ, Ansay T, Gq signaling is required for allergen-induced pulmonary eosinophilia. J Immunol 2002;168:3543–3549.
   PubMed Web of Science ®Google Scholar
• Jansen HM. The role of alveolar macrophages and dendritic cells in allergic airway sensitization. Allergy 1996;51:279–292.
   PubMedGoogle Scholar
• Gajewska BU, Tafuri A, Swirski FK, B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance. J Immunol 2005;174:3000–3005.
   PubMedGoogle Scholar
• Stampfli MR, Scott Neigh G, Wiley RE, Regulation of allergic mucosal sensitization by interleukin-12 gene transfer to the airway. Am J Respir Cell Mol Biol 1999;21:317–326.
   PubMedGoogle Scholar
• Swirski FK, Sajic D, Robbins CS, Chronic exposure to innocuous antigen in sensitized mice leads to suppressed airway eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor. J Immunol 2002;169:3499–3506.
   PubMedGoogle Scholar
• Bilyk N, Holt PG. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med 1993;177:1773–1777.
   PubMed Web of Science ®Google Scholar
• van Rijt LS, Prins JB, Leenen PJ, Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly-6C(neg) bone marrow precursors in a mouse model of asthma. Blood 2002;100:3663–3671.
   PubMedGoogle Scholar
• Lambrecht BN, Kleinjan A. Mouse models of asthma and rhinitis to study the role of dendritic cells in sensitization and development of inflammation Drug Discovery Today. Disease Models 2006;3:205–211.
   Google Scholar
• de Heer HJ, Hammad H, Soullie T, Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 2004;200:89–98.
   PubMed Web of Science ®Google Scholar
• Johnson JR, Wiley RE, Fattouh R, Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Respir Crit Care Med 2004;169:378–385.
   PubMed Web of Science ®Google Scholar
• Hammad H, Plantinga M, Deswarte K, Inflammatory dendritic cells –not basophils –are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med 2010;207:2097–2111.
   PubMed Web of Science ®Google Scholar
• Fattouh R, Pouladi MA, Alvarez D, House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation. Am J Respir Crit Care Med 2005;172:314–321.
   PubMedGoogle Scholar
• Hewitt CR, Brown AP, Hart BJ, Pritchard DI. A major house dust mite allergen disrupts the immunoglobulin E network by selectively cleaving CD23: innate protection by antiproteases. J Exp Med 1995;182:1537–1544.
   PubMed Web of Science ®Google Scholar
• Schulz O, Sewell HF, Shakib F. Proteolytic cleavage of CD25, the alpha subunit of the human T cell interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity. J Exp Med 1998;187:271–275.
   PubMed Web of Science ®Google Scholar
• Comoy EE, Pestel J, Duez C, The house dust mite allergen, Dermatophagoides pteronyssinus, promotes type 2 responses by modulating the balance between IL-4 and IFN-gamma. J Immunol 1998;160:2456–2462.
   PubMed Web of Science ®Google Scholar
• Hammad H, Chieppa M, Perros F, House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009;15:410–416.
   PubMed Web of Science ®Google Scholar
• Lewkowich IP, Day SB, Ledford JR, Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation. Respir Res 2011;12:122.
   PubMedGoogle Scholar
• Wan H, Winton HL, Soeller C, Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 1999;104:123–133.
   PubMed Web of Science ®Google Scholar
• Sun G, Stacey MA, Schmidt M, Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells. J Immunol 2001;167:1014–1021.
   PubMed Web of Science ®Google Scholar
• King C, Brennan S, Thompson PJ, Stewart GA. Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium. J Immunol 1998;161:3645–3651.
   PubMed Web of Science ®Google Scholar
• Willart MA, Deswarte K, Pouliot P, Interleukin-1alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med 209:1505–1517.
   PubMedGoogle Scholar
• Cohn L. Food for thought: can immunological tolerance be induced to treat asthma? Am J Respir Cell Mol Biol 2001;24:509–512.
   PubMedGoogle Scholar
• Roncarolo MG, Bacchetta R, Bordignon C, Type 1 T regulatory cells. Immunol Rev 2001;182:68–79.
   PubMed Web of Science ®Google Scholar
• Magnan A, van Pee D, Bongrand P, Vervloet D. Alveolar macrophage interleukin (IL)-10 and IL-12 production in atopic asthma. Allergy 1998;53:1092–1095.
   PubMedGoogle Scholar
• Tournoy KG, Hove C, Grooten J, Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma? Clin Exp Allergy 2006;36:8–20.
   PubMedGoogle Scholar
• Shevach EM. CD4 +CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2002;2:389–400.
   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. Nat Immunol 2001;2:725–731.
   PubMed Web of Science ®Google Scholar
• Terui T, Sano K, Shirota H, TGF-beta-producing CD4+ mediastinal lymph node cells obtained from mice tracheally tolerized to ovalbumin (OVA) suppress both Th1- and Th2-induced cutaneous inflammatory responses to OVA by different mechanisms. J Immunol 2001;167:3661–3667.
   PubMedGoogle Scholar
• Ritz SA, Gajewska BU, Stampfli MR, Jordana M. Determinants of the immune-inflammatory response in allergic airway inflammation: overview of antigen presentation and cellular activation. J Allergy Clin Immunol 2000;106:S206–S212.
   Google Scholar
• Stampfli MR, Cwiartka M, Gajewska BU, Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am J Respir Cell Mol Biol 1999;21:586–596.
   PubMed Web of Science ®Google Scholar
• Wang Y, McCusker C. Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: development of tolerance using environmental antigens. J Allergy Clin Immunol 2006;118:143–151.
   PubMed Web of Science ®Google Scholar
• Hall G, Houghton CG, Rahbek JU, Suppression of allergen reactive Th2 mediated responses and pulmonary eosinophilia by intranasal administration of an immunodominant peptide is linked to IL-10 production. Vaccine 2003;21:549–561.
   PubMedGoogle Scholar
• Wiedermann U, Jahn-Schmid B, Bohle B, Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type I allergy. J Allergy Clin Immunol 1999;103:1202–1210.
   PubMed Web of Science ®Google Scholar
• Unger WW, Hauet-Broere F, Jansen W, Early events in peripheral regulatory T cell induction via the nasal mucosa. J Immunol 2003;171:4592–4603.
   PubMedGoogle Scholar
• Brimnes MK, Bonifaz L, Steinman RM, Moran TM. Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered, normally nonimmunogenic protein. J Exp Med 2003;198:133–144.
   PubMed Web of Science ®Google Scholar
• Moerloose KB, Robays LJ, Maes T, Cigarette smoke exposure facilitates allergic sensitization in mice. Respir Res 2006;7:49.
   PubMed Web of Science ®Google Scholar
• Tsitoura DC, DeKruyff RH, Lamb JR, Umetsu DT. Intranasal exposure to protein antigen induces immunological tolerance mediated by functionally disabled CD4 +T cells. J Immunol 1999;163:2592–2600.
   PubMed Web of Science ®Google Scholar
• Tsitoura DC, Blumenthal RL, Berry G, Mechanisms preventing allergen-induced airways hyperreactivity: role of tolerance and immune deviation. J Allergy Clin Immunol 2000;106:239–246.
   PubMedGoogle Scholar
• Alvarez D, Swirski FK, Yang TC, Inhalation tolerance is induced selectively in thoracic lymph nodes but executed pervasively at distant mucosal and nonmucosal tissues. J Immunol 2006;176:2568–2580.
   PubMedGoogle Scholar
• Kearley J, Barker JE, Robinson DS, Lloyd CM. Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+ CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 2005;202:1539–1547.
   PubMed Web of Science ®Google Scholar
• Lewkowich IP, Herman NS, Schleifer KW, CD4+ CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med 2005;202:1549–1561.
   PubMed Web of Science ®Google Scholar
• Cederbom L, Hall H, Ivars F. CD4+ CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol 2000;30:1538–1543.
   PubMed Web of Science ®Google Scholar
• Piccirillo CA, Letterio JJ, Thornton AM, CD4(+) CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 2002;196:237–246.
   PubMed Web of Science ®Google Scholar
• Kabbur PM, Carson WF 4th, Guernsey L, Interleukin-10 does not mediate inhalational tolerance in a chronic model of ovalbumin-induced allergic airway disease. Cell Immunol 2006;239:67–74.
   PubMedGoogle Scholar
• Zuany-Amorim C, Haile S, Leduc D, Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice. J Clin Invest 1995;95:2644–2651.
   PubMed Web of Science ®Google Scholar
• Benson RA, Adamson K, Corsin-Jimenez M, Notch1 co-localizes with CD4 on activated T cells and Notch signaling is required for IL-10 production. Eur J Immunol 2005;35:859–869.
   PubMedGoogle Scholar
• Barbey C, Donatelli-Dufour N, Batard P, Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323–339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance. Clin Exp Allergy 2004;34:654–662.
   PubMedGoogle Scholar
• Zeller JC, Panoskaltsis-Mortari A, Murphy WJ, Induction of CD4 +T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-beta. J Immunol 1999;163:3684–3691.
   PubMed Web of Science ®Google Scholar
• Wolvers DA, Coenen-de Roo CJ, Mebius RE, Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: studies with OVA and human cartilage gp-39. J Immunol 1999;162:1994–1998.
   PubMed Web of Science ®Google Scholar
• Cottrez F, Hurst SD, Coffman RL, Groux H. T regulatory cells 1 inhibit a Th2-specific response in vivo. J Immunol 2000;165:4848–4853.
   PubMed Web of Science ®Google Scholar
• Schramm CM, Puddington L, Wu C, Chronic inhaled ovalbumin exposure induces antigen-dependent but not antigen-specific inhalational tolerance in a murine model of allergic airway disease. Am J Pathol 2004;164:295–304.
   PubMed Web of Science ®Google Scholar
• Van Hove CL, Maes T, Joos GF, Tournoy KG. Prolonged inhaled allergen exposure can induce persistent tolerance. Am J Respir Cell Mol Biol 2007;36:573–584.
   PubMed Web of Science ®Google Scholar
• Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol 2008;8:193–204.
   PubMed Web of Science ®Google Scholar
• Lambrecht BN, Hammad H. Biology of lung dendritic cells at the origin of asthma. Immunity 2009;31:412–424.
   PubMed Web of Science ®Google Scholar
• Barrat FJ, Cua DJ, Boonstra A, 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 2002;195:603–616.
   PubMed Web of Science ®Google Scholar
• Zuany-Amorim C, Manlius C, Trifilieff A, Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation. J Immunol 2002;169:1492–1499.
   PubMed Web of Science ®Google Scholar
• Stock P, Akbari O, Berry G, Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity. Nat Immunol 2004;5:1149–1156.
   PubMed Web of Science ®Google Scholar
• Renz H, Herz U. The bidirectional capacity of bacterial antigens to modulate allergy and asthma. Eur Respir J 2002;19:158–171.
   PubMedGoogle Scholar
• Hansen G, McIntire JJ, Yeung VP, CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation. J Clin Invest 2000;105:61–70.
   PubMed Web of Science ®Google Scholar
• Wan YY, Flavell RA. TGF-beta and regulatory T cell in immunity and autoimmunity. J Clin Immunol 2008;28:647–659.
   PubMed Web of Science ®Google Scholar
• Chen W, Jin W, Hardegen N, Conversion of peripheral CD4+ CD25–naive T cells to CD4+ CD25 +regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003;198:1875–1886.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+) CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 2001;194:629–644.
   PubMed Web of Science ®Google Scholar
• Thornton AM, Shevach EM. CD4+ CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998;188:287–296.
   PubMed Web of Science ®Google Scholar
• Ostroukhova M, Seguin-Devaux C, Oriss TB, Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J Clin Invest 2004;114:28–38.
   PubMed Web of Science ®Google Scholar
• Marco AJ, Domingo M, Ruberte J, Lymphatic drainage of Listeria monocytogenes and Indian ink inoculated in the peritoneal cavity of the mouse. Lab Anim 1992;26:200–205.
   PubMedGoogle Scholar
• Gajewska BU, Swirski FK, Alvarez D, Temporal-spatial analysis of the immune response in a murine model of ovalbumin-induced airways inflammation. Am J Respir Cell Mol Biol 2001;25:326–334.
   PubMed Web of Science ®Google Scholar
• Haneda K, Sano K, Tamura G, Transforming growth factor-beta secreted from CD4(+) T cells ameliorates antigen-induced eosinophilic inflammation. A novel high-dose tolerance in the trachea. Am J Respir Cell Mol Biol 1999;21:268–274.
   PubMed Web of Science ®Google Scholar
• Ludviksson BR, Seegers D, Resnick AS, Strober W. The effect of TGF-beta1 on immune responses of naive versus memory CD4+ Th1/Th2 T cells. Eur J Immunol 2000;30:2101–2111.
   PubMedGoogle Scholar
• Cottrez F, Groux H. Regulation of TGF-beta response during T cell activation is modulated by IL-10. J Immunol 2001;167:773–778.
   PubMed Web of Science ®Google Scholar
• Kitani A, Fuss I, Nakamura K, Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med 2003;198:1179–1188.
   PubMed Web of Science ®Google Scholar
• Do JS, Fink PJ, Li L, Cutting edge: spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF-beta 1-dependent mechanism. J Immunol 2010;184:1675–1679.
   PubMedGoogle Scholar
• Ostroukhova M, Qi Z, Oriss TB, Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-beta. J Clin Invest 2006;116:996–1004.
   PubMedGoogle Scholar
• Weaver CT, Harrington LE, Mangan PR, Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 2006;24:677–688.
   PubMed Web of Science ®Google Scholar
• Mangan PR, Harrington LE, O'Quinn DB, Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006;441:231–234.
   PubMed Web of Science ®Google Scholar
• Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 2000;118:1001–1011.
   PubMed Web of Science ®Google Scholar
• Becker C, Wirtz S, Blessing M, Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Invest 2003;112:693–706.
   PubMed Web of Science ®Google Scholar
• Veldhoen M, Hocking RJ, Atkins CJ, TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006;24:179–189.
   PubMed Web of Science ®Google Scholar
• Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+ CD25+ regulatory T cells. J Exp Med 2005;201:1061–1067.
   PubMed Web of Science ®Google Scholar
• Okamoto M, Matsuda H, Joetham A, Jagged1 on dendritic cells and Notch on CD4+ T cells initiate lung allergic responsiveness by inducing IL-4 production. J Immunol 2009;183:2995–3003.
   PubMed Web of Science ®Google Scholar
• Radtke F, Fasnacht N, Macdonald HR. Notch signaling in the immune system. Immunity 2010;32:14–27.
   PubMed Web of Science ®Google Scholar
• Amsen D, Antov A, Jankovic D, Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 2007;27:89–99.
   PubMed Web of Science ®Google Scholar
• Tanigaki K, Tsuji M, Yamamoto N, Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity 2004;20:611–622.
   PubMed Web of Science ®Google Scholar
• Wolfer A, Wilson A, Nemir M, Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta lineage thymocytes. Immunity 2002;16:869–879.
   PubMed Web of Science ®Google Scholar
• Kang JH, Kim BS, Uhm TG, Gamma-secretase inhibitor reduces allergic pulmonary inflammation by modulating Th1 and Th2 responses. Am J Respir Crit Care Med 2009;179:875–882.
   PubMed Web of Science ®Google Scholar
• Fang TC, Yashiro-Ohtani Y, Del Bianco C, Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity 2007;27:100–110.
   PubMed Web of Science ®Google Scholar
• Amsen D, Blander JM, Lee GR, Instruction of distinct CD4 T helper cell fates by different Notch ligands on antigen-presenting cells. Cell 2004;117:515–526.
   PubMed Web of Science ®Google Scholar
• Tu L, Fang TC, Artis D, Notch signaling is an important regulator of type 2 immunity. J Exp Med 2005;202:1037–1042.
   PubMed Web of Science ®Google Scholar
• Okamoto M, Takeda K, Lucas JJ, Low-dose lipopolysaccharide affects lung allergic responses by regulating Jagged1 expression on antigen-pulsed dendritic cells. Int Arch Allergy Immunol 2012;157:65–72.
   PubMedGoogle Scholar
• Skokos D, Nussenzweig MC. CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J Exp Med 2007;204:1525–1531.
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Schaller MA, Neupane R, Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. J Immunol 2009;182:7381–7388.
   PubMed Web of Science ®Google Scholar
• Fukushima A, Sumi T, Ishida W, Notch ligand Delta-like4 inhibits the development of murine experimental allergic conjunctivitis. Immunol Lett 2008;121:140–147.
   PubMedGoogle Scholar
• Sun J, Krawczyk CJ, Pearce EJ. Suppression of Th2 cell development by Notch ligands Delta1 and Delta4. J Immunol 2008;180:1655–1661.
   PubMed Web of Science ®Google Scholar
• Krawczyk CM, Sun J, Pearce EJ. Th2 differentiation is unaffected by Jagged2 expression on dendritic cells. J Immunol 2008;180:7931–7937.
   PubMed Web of Science ®Google Scholar
• Worsley AG, LeibundGut-Landmann S, Slack E, Dendritic cell expression of the Notch ligand Jagged2 is not essential for Th2 response induction in vivo. Eur J Immunol 2008;38:1043–1049.
   PubMed Web of Science ®Google Scholar
• Jang S, Schaller M, Berlin AA, Lukacs NW. Notch ligand delta-like 4 regulates development and pathogenesis of allergic airway responses by modulating IL-2 production and Th2 immunity. J Immunol 2010;185:5835–5844.
   PubMedGoogle Scholar
• Hoyne GF, Tan K, Corsin-Jimenez M, Immunological tolerance to inhaled antigen. Am J Respir Crit Care Med 2000;162:S169–S174.
   PubMed Web of Science ®Google Scholar
• Tan AM, Chen HC, Pochard P, TLR4 signaling in stromal cells is critical for the initiation of allergic Th2 responses to inhaled antigen. J Immunol 2010;184:3535–3544.
   PubMedGoogle Scholar
• Washburn T, Schweighoffer E, Gridley T, Notch activity influences the alphabeta versus gammadelta T cell lineage decision. Cell 1997;88:833–843.
   PubMed Web of Science ®Google Scholar
• Ciofani M, Zuniga-Pflucker JC. Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 2005;6:881–888.
   PubMed Web of Science ®Google Scholar
• Lauritsen JP, Wong GW, Lee SY, Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity 2009;31:565–575.
   PubMedGoogle Scholar
• Hoyne GF, Dallman MJ, Lamb JR. T-cell regulation of peripheral tolerance and immunity: the potential role for Notch signalling. Immunology 2000;100:281–288.
   PubMedGoogle Scholar
• Murata A, Okuyama K, Sakano S A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells. J Immunol 2010;185:3905–3912.
   PubMedGoogle Scholar
• Schaller MA, Neupane R, Rudd BD, Notch ligand Delta-like 4 regulates disease pathogenesis during respiratory viral infections by modulating Th2 cytokines. J Exp Med 2007;204:2925–2934.
   PubMed Web of Science ®Google Scholar
• Krishnamoorthy N, Oriss TB, Paglia M, Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Nat Med 2008;14:565–573.
   PubMed Web of Science ®Google Scholar
• Ray P, Krishnamoorthy N, Ray A. Emerging functions of c-kit and its ligand stem cell factor in dendritic cells: regulators of T cell differentiation. Cell Cycle 2008;7:2826–2832.
   PubMed Web of Science ®Google Scholar
• Raymond T, Schaller M, Hogaboam CM, Toll-like receptors, Notch ligands, and cytokines drive the chronicity of lung inflammation. Proc Am Thorac Soc 2007;4:635–641.
   PubMedGoogle Scholar
• Hoyne GF, Askonas BA, Hetzel C, Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. Int Immunol 1996;8:335–342.
   PubMed Web of Science ®Google Scholar
• Seymour BW, Gershwin LJ, Coffman RL. Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-gamma/delta +T cells or interferon (IFN)-gamma in a murine model of allergen sensitization. J Exp Med 1998;187:721–731.
   PubMed Web of Science ®Google Scholar
• Perez VL, Van Parijs L, Biuckians A, Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 1997;6:411–417.
   PubMed Web of Science ®Google Scholar
• Wiley R, Palmer K, Gajewska B, Expression of the Th1 chemokine IFN-gamma-inducible protein 10 in the airway alters mucosal allergic sensitization in mice. J Immunol 2001;166:2750–2759.
   PubMedGoogle Scholar
• Akbari O, Freeman GJ, Meyer EH, Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002;8:1024–1032.
   PubMed Web of Science ®Google Scholar
• Gonzalo JA, Tian J, Delaney T, ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses. Nat Immunol 2001;2:597–604.
   PubMed Web of Science ®Google Scholar
• Kohl J, Baelder R, Lewkowich IP, A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. J Clin Invest 2006;116:783–796.
   PubMed Web of Science ®Google Scholar
• Lambrecht BN. An unexpected role for the anaphylatoxin C5a receptor in allergic sensitization. J Clin Invest 2006;116:628–632.
   PubMedGoogle Scholar
• McMenamin C, McKersey M, Kuhnlein P, Gamma delta T cells down-regulate primary IgE responses in rats to inhaled soluble protein antigens. J Immunol 1995;154:4390–4394.
   PubMedGoogle Scholar
• McMenamin C, Oliver J, Girn B, Regulation of T-cell sensitization at epithelial surfaces in the respiratory tract: suppression of IgE responses to inhaled antigens by CD3 +Tcr alpha-/beta- lymphocytes (putative gamma/delta T cells). Immunology 1991;74:234–239.
   PubMedGoogle Scholar
• McMenamin C, Pimm C, McKersey M, Holt PG. Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells. Science 1994;265:1869–1871.
   PubMed Web of Science ®Google Scholar
• Svensson L, Lilliehook B, Larsson R, Bucht A. Gammadelta T cells contribute to the systemic immunoglobulin E response and local B-cell reactivity in allergic eosinophilic airway inflammation. Immunology 2003;108:98–108.
   PubMed Web of Science ®Google Scholar
• Phipps S, Hansbro N, Lam CE, Allergic sensitization is enhanced in early life through toll-like receptor 7 activation. Clin Exp Allergy 2009;39:1920–1928.
   PubMed Web of Science ®Google Scholar
• Phipps S, Lam CE, Kaiko GE, Toll/IL-1 signaling is critical for house dust mite-specific helper T cell type 2 and type 17 [corrected] responses. Am J Respir Crit Care Med 2009;179:883–893.
   PubMed Web of Science ®Google Scholar
• Piggott DA, Eisenbarth SC, Xu L, MyD88-dependent induction of allergic Th2 responses to intranasal antigen. J Clin Invest 2005;115:459–467.
   PubMed Web of Science ®Google Scholar
• Eisenbarth SC, Piggott DA, Huleatt JW, Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 2002;196:1645–1651.
   PubMed Web of Science ®Google Scholar
• Hollingsworth JW, Whitehead GS, Lin KL, TLR4 signaling attenuates ongoing allergic inflammation. J Immunol 2006;176:5856–5862.
   PubMed Web of Science ®Google Scholar