Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

References

• Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018;378(19):1811–1823. doi:10.1056/NEJMra170575129742380
   PubMed Web of Science ®Google Scholar
• Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.21471066
   PubMed Web of Science ®Google Scholar
• King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A Phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–2092. doi:10.1056/NEJMoa140258224836312
   PubMed Web of Science ®Google Scholar
• Richeldi L, Du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–2082. doi:10.1056/NEJMoa140258424836310
   PubMed Web of Science ®Google Scholar
• Evans CM, Fingerlin TE, Schwarz MI, et al. Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways. Physiol Rev. 2016;96(4):1567–1591. doi:10.1152/physrev.00004.201627630174
   PubMed Web of Science ®Google Scholar
• Wuyts WA, Agostini C, Antoniou KM, et al. The pathogenesis of pulmonary fibrosis: a moving target. Eur Respir J. 2013;41(5):1207–1218. doi:10.1183/09031936.0007301223100500
   PubMed Web of Science ®Google Scholar
• Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32. doi:10.1186/s12931-018-0730-229471816
   PubMed Web of Science ®Google Scholar
• Taskar VS, Coultas DB. Is idiopathic pulmonary fibrosis an environmental disease? Proc Am Thorac Soc. 2006;3(4):293–298. doi:10.1513/pats.200512-131TK16738192
   PubMedGoogle Scholar
• Kropski JA, Blackwell TS, Loyd JE. The genetic basis of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(6):1717–1727. doi:10.1183/09031936.0016381425837031
   PubMed Web of Science ®Google Scholar
• Kaur A, Mathai SK, Schwartz DA. Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment. Front Med. 2017;4:154. doi:10.3389/fmed.2017.00154
   PubMed Web of Science ®Google Scholar
• Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364(16):1503–1512. doi:10.1056/NEJMoa101366021506741
   PubMed Web of Science ®Google Scholar
• Zhang Y, Noth I, Garcia JGN, Kaminski N. A Variant in the Promoter of MUC5B and Idiopathic Pulmonary Fibrosis. N Engl J Med. 2011;364(16):1576–1577. doi:10.1056/NEJMc101350421506748
   PubMed Web of Science ®Google Scholar
• Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45(6):613–620. doi:10.1038/ng.260923583980
   PubMed Web of Science ®Google Scholar
• Noth I, Zhang Y, Ma SF, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1(4):309–317. doi:10.1016/s2213-2600(13)70045-624429156
   PubMed Web of Science ®Google Scholar
• Stock CJ, Sato H, Fonseca C, et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax. 2013;68(5):436–441. doi:10.1136/thoraxjnl-2012-20178623321605
   PubMed Web of Science ®Google Scholar
• Borie R, Crestani B, Dieude P, et al. The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population. PLoS One. 2013;8 (8):e70621. doi:10.1371/journal.pone.007062123940607
   PubMed Web of Science ®Google Scholar
• Peljto AL, Selman M, Kim DS, et al. The MUC5B promoter polymorphism is associated with idiopathic pulmonary fibrosis in a Mexican cohort but is rare among Asian ancestries. Chest. 2015;147(2):460–464.25275363
   PubMed Web of Science ®Google Scholar
• Yang IV, Fingerlin TE, Evans CM, Schwarz MI, Schwartz DA. MUC5B and Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2015;12 Suppl 2(Suppl 2):S193–S199. doi:10.1513/AnnalsATS.201503-110AW26595739
   PubMedGoogle Scholar
• Horimasu Y, Ohshimo S, Bonella F, et al. MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology. 2015;20(3):439–444. doi:10.1111/resp.1246625581455
   PubMed Web of Science ®Google Scholar
• Moore C, Blumhagen RZ, Yang IV, et al. Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019;200(2):199–208. doi:10.1164/rccm.201810-1891OC31034279
   PubMed Web of Science ®Google Scholar
• Allen RJ, Guillen-Guio B, Oldham JM, et al. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020;201(5):564–574. doi:10.1164/rccm.201905-1017OC31710517
   PubMed Web of Science ®Google Scholar
• Idiopathic Pulmonary Fibrosis Clinical Research. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968–1977. doi:10.1056/NEJMoa111335422607134
   PubMed Web of Science ®Google Scholar
• Bringardner BD, Baran CP, Eubank TD, Marsh CB. The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis. Antioxid Redox Signal. 2008;10(2):287–301. doi:10.1089/ars.2007.189717961066
   PubMed Web of Science ®Google Scholar
• Desai O, Winkler J, Minasyan M, Herzog EL. The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis. Front Med. 2018;5:43. doi:10.3389/fmed.2018.00043
   PubMed Web of Science ®Google Scholar
• Heukels P, Moor CC, von der Thüsen JH, Wijsenbeek MS, Kool M. Inflammation and immunity in IPF pathogenesis and treatment. Respir Med. 2019;147:79–91. doi:10.1016/j.rmed.2018.12.01530704705
   PubMed Web of Science ®Google Scholar
• Warheit-Niemi HI, Hult EM, Moore BB. A pathologic two-way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity. Clin Transl Immunology. 2019;8(6):e1065. doi:10.1002/cti2.106531293783
   PubMed Web of Science ®Google Scholar
• Kolahian S, Fernandez IE, Eickelberg O, Hartl D. Immune Mechanisms in Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2016;55(3):309–322. doi:10.1165/rcmb.2016-0121TR27149613
   PubMed Web of Science ®Google Scholar
• Parker D, Prince A. Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol. 2011;45(2):189–201. doi:10.1165/rcmb.2011-0011RT21330463
   PubMed Web of Science ®Google Scholar
• Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363(23):2233–2247. doi:10.1056/NEJMra091006121121836
   PubMed Web of Science ®Google Scholar
• Adler KB, Tuvim MJ, Dickey BF. Regulated mucin secretion from airway epithelial cells. Front Endocrinol (Lausanne). 2013;4:129. doi:10.3389/fendo.2013.0012924065956
   PubMedGoogle Scholar
• Kuek LE, Lee RJ. First contact: the role of respiratory cilia in host-pathogen interactions in the airways. Am J Respir Cell Mol Biol. 2020;319(4):L603–L619. doi:10.1152/ajplung.00283.2020
   Web of Science ®Google Scholar
• Ganz T. Antimicrobial polypeptides in host defense of the respiratory tract. J Clin Invest. 2002;109(6):693–697. doi:10.1172/JCI1521811901174
   PubMed Web of Science ®Google Scholar
• Frey A, Lunding LP, Ehlers JC, Weckmann M, Zissler UM, Wegmann M. More Than Just a Barrier: the Immune Functions of the Airway Epithelium in Asthma Pathogenesis. Front Immunol. 2020;11(761). doi:10.3389/fimmu.2020.00761
   Web of Science ®Google Scholar
• Davies DE. Epithelial barrier function and immunity in asthma. Ann Am Thorac Soc. 2014;11(Suppl 5):S244–251. doi:10.1513/AnnalsATS.201407-304AW25525727
   PubMedGoogle Scholar
• Hiemstra PS, McCray PB Jr, Bals R. The innate immune function of airway epithelial cells in inflammatory lung disease. Eur Respir J. 2015;45(4):1150–1162. doi:10.1183/09031936.0014151425700381
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Akira S. Pattern Recognition Receptors and Inflammation. Cell. 2010;140(6):805–820. doi:10.1016/j.cell.2010.01.02220303872
   PubMed Web of Science ®Google Scholar
• Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31(3):358–364. doi:10.1165/rcmb.2003-0388OC15191912
   PubMed Web of Science ®Google Scholar
• Hartl D, Tirouvanziam R, Laval J, et al. Innate Immunity of the Lung: from Basic Mechanisms to Translational Medicine. J Innate Immun. 2018;10(5–6):487–501. doi:10.1159/00048705729439264
   PubMed Web of Science ®Google Scholar
• Martin TR, Frevert CW. Innate immunity in the lungs. Proc Am Thorac Soc. 2005;2(5):403–411. doi:10.1513/pats.200508-090JS16322590
   PubMedGoogle Scholar
• Byrne AJ, Mathie SA, Gregory LG, Lloyd CM. Pulmonary macrophages: key players in the innate defence of the airways. Thorax. 2015;70(12):1189–1196. doi:10.1136/thoraxjnl-2015-20702026286722
   PubMed Web of Science ®Google Scholar
• Peljto AL, Zhang Y, Fingerlin TE, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013;309(21):2232–2239. doi:10.1001/jama.2013.582723695349
   PubMed Web of Science ®Google Scholar
• Biondini D, Balestro E, Rigobello C, et al. MUC5B genotype affects survival of patients with idiopathic pulmonary fibrosis (IPF) on antifibrotic treatment. Eur Respir J. 2019;54(suppl63):PA1352. doi:10.1183/13993003.congress-2019.PA1352
   Web of Science ®Google Scholar
• Dudbridge F, Allen RJ, Sheehan NA, et al. Adjustment for index event bias in genome-wide association studies of subsequent events. Nat Commun. 2019;10(1):1561. doi:10.1038/s41467-019-09381-w30952951
   PubMedGoogle Scholar
• van der Vis JJ, Snetselaar R, Kazemier KM, Ten Klooster L, Grutters JC, van Moorsel CH. Effect of Muc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias. Respirology. 2016;21(4):712–717. doi:10.1111/resp.1272826699835
   PubMed Web of Science ®Google Scholar
• Newton CA, Oldham JM, Ley B, et al. Telomere length and genetic variant associations with interstitial lung disease progression and survival. Eur Respir J. 2019;53(4):1801641. doi:10.1183/13993003.01641-201830635297
   PubMed Web of Science ®Google Scholar
• Ley B, Newton CA, Arnould I, et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med. 2017;5(8):639–647. doi:10.1016/S2213-2600(17)30216-328648751
   PubMed Web of Science ®Google Scholar
• Helling BA, Gerber AN, Kadiyala V, et al. Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2017;57(1):91–99. doi:10.1165/rcmb.2017-0046OC28272906
   PubMed Web of Science ®Google Scholar
• Stock CJ, Conti C, Montero-Fernandez Á, et al. Interaction between the promoter MUC5B polymorphism and mucin expression: is there a difference according to ILD subtype? Thorax. 2020;75(10):901–903. doi:10.1136/thoraxjnl-2020-21457932580994
   PubMed Web of Science ®Google Scholar
• Nakano Y, Yang IV, Walts AD, et al. MUC5B Promoter Variant rs35705950 Affects MUC5B Expression in the Distal Airways in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2016;193(4):464–466. doi:10.1164/rccm.201509-1872LE26871673
   PubMed Web of Science ®Google Scholar
• Okuda K, Chen G, Subramani DB, et al. Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. Am J Respir Crit Care Med. 2019;199(6):715–727. doi:10.1164/rccm.201804-0734OC30352166
   PubMed Web of Science ®Google Scholar
• Seibold MA, Smith RW, Urbanek C, et al. The idiopathic pulmonary fibrosis honeycomb cyst contains a mucociliary pseudostratified epithelium. PLoS One. 2013;8(3):e58658–e58658. doi:10.1371/journal.pone.005865823527003
   PubMed Web of Science ®Google Scholar
• Bonser LR, Erle DJ. Airway Mucus and Asthma: the Role of MUC5AC and MUC5B. J Clin Med. 2017;6:12. doi:10.3390/jcm6120112
   PubMed Web of Science ®Google Scholar
• Roy MG, Livraghi-Butrico A, Fletcher AA, et al. Muc5b is required for airway defence. Nature. 2014;505(7483):412–416. doi:10.1038/nature1280724317696
   PubMed Web of Science ®Google Scholar
• Bhowmik A, Chahal K, Austin G, Chakravorty I. Improving mucociliary clearance in chronic obstructive pulmonary disease. Respir Med. 2009;103(4):496–502. doi:10.1016/j.rmed.2008.10.01419091536
   PubMed Web of Science ®Google Scholar
• Mall MA. Unplugging Mucus in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2016;13(Suppl 2):S177–185. doi:10.1513/AnnalsATS.201509-641KV27115954
   PubMed Web of Science ®Google Scholar
• Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002;33(4):293–306. doi:10.1002/ppul.1007911921459
   PubMed Web of Science ®Google Scholar
• Kreda SM, Davis CW, Rose MC. CFTR, mucins, and mucus obstruction in cystic fibrosis. Cold Spring Harb Perspect Med. 2012;2(9):a009589–a009589. doi:10.1101/cshperspect.a00958922951447
   PubMed Web of Science ®Google Scholar
• Hancock LA, Hennessy CE, Solomon GM, et al. Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice. Nat Commun. 2018;9(1):5363. doi:10.1038/s41467-018-07768-930560893
   PubMedGoogle Scholar
• Baumgartner KB, Samet JM, Stidley CA, Colby TV, Waldron JA. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1997;155(1):242–248. doi:10.1164/ajrccm.155.1.90013199001319
   PubMed Web of Science ®Google Scholar
• Baumgartner KB, Samet JM, Coultas DB, et al. Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Am J Epidemiol. 2000;152(4):307–315.10968375
   PubMed Web of Science ®Google Scholar
• Paolocci G, Folletti I, Torén K, et al. Occupational risk factors for idiopathic pulmonary fibrosis in Southern Europe: a case-control study. BMC Pulm Med. 2018;18(1):75. doi:10.1186/s12890-018-0644-229784045
   PubMedGoogle Scholar
• Molyneaux PL, Cox MJ, Willis-Owen SA, et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190(8):906–913. doi:10.1164/rccm.201403-0541OC25184687
   PubMed Web of Science ®Google Scholar
• Han MK, Zhou Y, Murray S, et al. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respir Med. 2014;2(7):548–556. doi:10.1016/s2213-2600(14)70069-424767767
   PubMed Web of Science ®Google Scholar
• O’Dwyer D, Ashley N, Gurczynski SL, et al. Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019;199(9):1127–1138. doi:10.1164/rccm.201809-1650OC30789747
   PubMed Web of Science ®Google Scholar
• Invernizzi R, Wu BG, Barnett J, et al. The Respiratory Microbiome in Chronic Hypersensitivity Pneumonitis is Distinct from that of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020. doi:10.1164/rccm.202002-0460OC
   Web of Science ®Google Scholar
• Invernizzi R, Barnett J, Rawal B, et al. Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent. Eur Respir J. 2020;1901519. doi:10.1183/13993003.01519-2019
   Web of Science ®Google Scholar
• Mathai SK, Pedersen BS, Smith K, et al. Desmoplakin Variants Are Associated with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2016;193(10):1151–1160. doi:10.1164/rccm.201509-1863OC26669357
   PubMed Web of Science ®Google Scholar
• Hao Y, Bates S, Mou H, et al. GWAS Functional Variant rs2076295 Regulates Desmoplakin (DSP) Expression in Airway Epithelial Cells. Am J Respir Crit Care Med. 2020. doi:10.1164/rccm.201910-1958OC
   Web of Science ®Google Scholar
• Polivka L, Hadj-Rabia S, Bal E, et al. Epithelial barrier dysfunction in desmoglein-1 deficiency. J Allergy Clin Immunol. 2018;142(2):702–706.e707. doi:10.1016/j.jaci.2018.04.00729705242
   PubMed Web of Science ®Google Scholar
• Coyne CB, Vanhook MK, Gambling TM, Carson JL, Boucher RC, Johnson LG. Regulation of airway tight junctions by proinflammatory cytokines. Mol Biol Cell. 2002;13(9):3218–3234. doi:10.1091/mbc.e02-03-013412221127
   PubMed Web of Science ®Google Scholar
• Jevnikar Z, Östling J, Ax E, et al. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation. J Allergy Clin Immunol. 2019;143(2):577–590. doi:10.1016/j.jaci.2018.05.02629902480
   PubMed Web of Science ®Google Scholar
• Ioannidis I, Ye F, McNally B, Willette M, Flaño E. Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J Virol. 2013;87(6):3261–3270. doi:10.1128/JVI.01956-1223302870
   PubMed Web of Science ®Google Scholar
• Beisswenger C, Lysenko ES, Weiser JN. Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium. Infect Immun. 2009;77(5):2212. doi:10.1128/IAI.01224-0819255194
   PubMed Web of Science ®Google Scholar
• Karampitsakos T, Woolard T, Bouros D, Tzouvelekis A. Toll-like receptors in the pathogenesis of pulmonary fibrosis. Eur J Pharmacol. 2017;808:35–43. doi:10.1016/j.ejphar.2016.06.04527364757
   PubMed Web of Science ®Google Scholar
• Samara KD, Antoniou KM, Karagiannis K, et al. Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis. Int J Oncol. 2012;40(5):1397–1404. doi:10.3892/ijo.2012.137422344343
   PubMed Web of Science ®Google Scholar
• Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461. doi:10.3389/fimmu.2014.0046125309543
   PubMed Web of Science ®Google Scholar
• Zhang G, Ghosh S. Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem. 2002;277(9):7059–7065. doi:10.1074/jbc.M10953720011751856
   PubMed Web of Science ®Google Scholar
• Li X, Kim SE, Chen T-Y, et al. Toll interacting protein protects bronchial epithelial cells from bleomycin-induced apoptosis. FASEB J. 2020;34(8):9884–9898. doi:10.1096/fj.201902636RR32596871
   PubMed Web of Science ®Google Scholar
• Didierlaurent A, Brissoni B, Velin D, et al. Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide. Mol Cell Biol. 2006;26(3):735–742. doi:10.1128/MCB.26.3.735-742.200616428431
   PubMed Web of Science ®Google Scholar
• Shah JA, Vary JC, Chau TT, et al. Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. J Immunol. 2012;189(4):1737–1746. doi:10.4049/jimmunol.110354122778396
   PubMed Web of Science ®Google Scholar
• Go H, Koh J, Kim HS, Jeon YK, Chung DH. Expression of toll-like receptor 2 and 4 is increased in the respiratory epithelial cells of chronic idiopathic interstitial pneumonia patients. Respir Med. 2014;108(5):783–792. doi:10.1016/j.rmed.2013.12.00724613046
   PubMed Web of Science ®Google Scholar
• Kurosaki F, Uchibori R, Sehara Y, et al. AAV6-Mediated IL-10 Expression in the Lung Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice. Hum Gene Ther. 2018;29(11):1242–1251. doi:10.1089/hum.2018.02429598007
   PubMed Web of Science ®Google Scholar
• Zhu L, Wang L, Luo X, et al. Tollip, an intracellular trafficking protein, is a novel modulator of the transforming growth factor-β signaling pathway. J Biol Chem. 2012;287(47):39653–39663. doi:10.1074/jbc.M112.38800923027871
   PubMed Web of Science ®Google Scholar
• van der Mark VA, Ghiboub M, Marsman C, et al. Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4. Cell Mol Life Sci. 2017;74(4):715–730. doi:10.1007/s00018-016-2360-527628304
   PubMed Web of Science ®Google Scholar
• Trujillo G, Meneghin A, Flaherty KR, et al. TLR9 differentiates rapidly from slowly progressing forms of idiopathic pulmonary fibrosis. Sci Transl Med. 2010;2(57):57ra82. doi:10.1126/scitranslmed.3001510
   PubMed Web of Science ®Google Scholar
• Bueno M, Zank D, Buendia-Roldán I, et al. PINK1 attenuates mtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses. PLoS One. 2019;14(6):e0218003–e0218003. doi:10.1371/journal.pone.021800331170232
   PubMed Web of Science ®Google Scholar
• Borthwick LA. The IL-1 cytokine family and its role in inflammation and fibrosis in the lung. Semin Immunopathol. 2016;38(4):517–534. doi:10.1007/s00281-016-0559-z27001429
   PubMed Web of Science ®Google Scholar
• Cohen P. The TLR and IL-1 signalling network at a glance. J Cell Sci. 2014;127(11):2383–2390. doi:10.1242/jcs.14983124829146
   PubMed Web of Science ®Google Scholar
• Korthagen NM, van Moorsel CHM, Kazemier KM, Ruven HJT, Grutters JC. IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study. Immunogenetics. 2012;64(5):371–377. doi:10.1007/s00251-012-0604-622322675
   PubMed Web of Science ®Google Scholar
• Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J. Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest. 2001;107(12):1529–1536. doi:10.1172/JCI1256811413160
   PubMed Web of Science ®Google Scholar
• Kline JN, Schwartz DA, Monick MM, Floerchinger CS, Hunninghake GW. Relative Release of lnterleukin-1β and lnterleukin-1 Receptor Antagonist by Alveolar Macrophages: A Study in Asbestos-Induced Lung Disease, Sarcoidosis, and Idiopathic Pulmonary Fibrosis. Chest. 1993;104(1):47–53. doi:10.1378/chest.104.1.478325116
   PubMed Web of Science ®Google Scholar
• Piguet PF, Vesin C, Grau GE, Thompson RC. Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. Cytokine. 1993;5(1):57–61. doi:10.1016/1043-4666(93)90024-y7683505
   PubMed Web of Science ®Google Scholar
• Cavalli G, Fallanca F, Dinarello CA, Dagna L. Treating pulmonary silicosis by blocking interleukin 1. Am J Respir Crit Care Med. 2015;191(5):596–598. doi:10.1164/rccm.201412-2150LE25723826
   PubMed Web of Science ®Google Scholar
• Sommariva M, Le Noci V, Bianchi F, et al. The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy. Cell Mol Life Sci. 2020;77(14):2739–2749. doi:10.1007/s00018-020-03452-831974656
   PubMed Web of Science ®Google Scholar
• Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis. Cell. 2004;118(2):229–241. doi:10.1016/j.cell.2004.07.00215260992
   PubMed Web of Science ®Google Scholar
• Yang D, Chen X, Wang J, et al. Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles. Immunity. 2019;50(3):692–706.e697. doi:10.1016/j.immuni.2019.02.00130824326
   PubMed Web of Science ®Google Scholar
• O’Dwyer DN, Armstrong ME, Trujillo G, et al. The Toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2013;188(12):1442–1450. doi:10.1164/rccm.201304-0760OC24070541
   PubMed Web of Science ®Google Scholar
• Hodgson U, Pulkkinen V, Dixon M, et al. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis. Am J Hum Genet. 2006;79(1):149–154. doi:10.1086/50463916773575
   PubMed Web of Science ®Google Scholar
• Pulkkinen V, Bruce S, Rintahaka J, et al. ELMOD2, a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses. FASEB J. 2010;24(4):1167–1177. doi:10.1096/fj.09-13854519966137
   PubMed Web of Science ®Google Scholar
• Azuma A, Li YJ, Abe S, et al. Interferon-{beta} inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-{beta} and thrombospondin. Am J Respir Cell Mol Biol. 2005;32(2):93–98. doi:10.1165/rcmb.2003-0374OC15557019
   PubMed Web of Science ®Google Scholar
• Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2004;350(2):125–133. doi:10.1056/NEJMoa03051114711911
   PubMed Web of Science ®Google Scholar
• Vergnon JM, Vincent M, de Thé G, Mornex JF, Weynants P, Brune J. Cryptogenic fibrosing alveolitis and Epstein-Barr virus: an association? Lancet. 1984;2(8406):768–771. doi:10.1016/s0140-6736(84)90702-56148520
   PubMed Web of Science ®Google Scholar
• Kelly BG, Lok SS, Hasleton PS, Egan JJ, Stewart JP. A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002;166(4):510–513. doi:10.1164/rccm.210305812186829
   PubMed Web of Science ®Google Scholar
• Wootton SC, Kim DS, Kondoh Y, et al. Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(12):1698–1702. doi:10.1164/rccm.201010-1752OC21471095
   PubMed Web of Science ®Google Scholar
• Yonemaru M, Kasuga I, Kusumoto H, et al. Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis. Eur Respir J. 1997;10(9):2040–2045. doi:10.1183/09031936.97.100920409311499
   PubMed Web of Science ®Google Scholar
• Malizia AP, Keating DT, Smith SM, Walls D, Doran PP, Egan JJ. Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFbeta1 expression. Am J Physiol Lung Cell Mol Physiol. 2008;295(3):L451–460. doi:10.1152/ajplung.00376.200718621908
   PubMed Web of Science ®Google Scholar
• Lok SS, Haider Y, Howell D, Stewart JP, Hasleton PS, Egan JJ. Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice. Eur Respir J. 2002;20(5):1228–1232. doi:10.1183/09031936.02.0027290212449178
   PubMed Web of Science ®Google Scholar
• Vannella KM, Luckhardt TR, Wilke CA, van Dyk LF, Toews GB, Moore BB. Latent herpesvirus infection augments experimental pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181(5):465–477. doi:10.1164/rccm.200905-0798OC20185751
   PubMed Web of Science ®Google Scholar
• Ebrahimi B, Dutia BM, Brownstein DG, Nash AA. Murine gammaherpesvirus-68 infection causes multi-organ fibrosis and alters leukocyte trafficking in interferon-gamma receptor knockout mice. Am J Pathol. 2001;158(6):2117–2125. doi:10.1016/s0002-9440(10)64683-411395389
   PubMed Web of Science ®Google Scholar
• Isler JA, Skalet AH, Alwine JC. Human cytomegalovirus infection activates and regulates the unfolded protein response. J Virol. 2005;79(11):6890–6899. doi:10.1128/JVI.79.11.6890-6899.200515890928
   PubMed Web of Science ®Google Scholar
• Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc. 2007;4(3):252–257. doi:10.1513/pats.200701-018AW17607008
   PubMedGoogle Scholar
• Han S, Mallampalli RK. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Ann Am Thorac Soc. 2015;12(5):765–774. doi:10.1513/AnnalsATS.201411-507FR25742123
   PubMed Web of Science ®Google Scholar
• Takezaki A, Tsukumo S, Setoguchi Y, et al. A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis. J Exp Med. 2019;216(12):2724–2735. doi:10.1084/jem.2018235131601679
   PubMed Web of Science ®Google Scholar
• Doubková M, Staňo Kozubík K, Radová L, et al. A novel germline mutation of the SFTPA1 gene in familial interstitial pneumonia. Hum Genome Var. 2019;6(1):12. doi:10.1038/s41439-019-0044-z30854216
   PubMedGoogle Scholar
• Wang Y, Kuan PJ, Xing C, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84(1):52–59. doi:10.1016/j.ajhg.2008.11.01019100526
   PubMed Web of Science ®Google Scholar
• McCormack FX, King TE Jr, Voelker DR, Robinson PC, Mason RJ. Idiopathic pulmonary fibrosis. Abnormalities in the bronchoalveolar lavage content of surfactant protein A. Am Rev Respir Dis. 1991;144(1):160–166. doi:10.1164/ajrccm/144.1.1602064123
   PubMedGoogle Scholar
• McCormack FX, King TE Jr, Bucher BL, Nielsen L, Mason RJ. Surfactant protein A predicts survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1995;152(2):751–759. doi:10.1164/ajrccm.152.2.76337387633738
   PubMed Web of Science ®Google Scholar
• LeVine AM, Whitsett JA, Gwozdz JA, et al. Distinct Effects of Surfactant Protein A or D Deficiency During Bacterial Infection on the Lung. J Immunol. 2000;165(7):3934. doi:10.4049/jimmunol.165.7.393411034401
   PubMed Web of Science ®Google Scholar
• Goto H, Ledford JG, Mukherjee S, Noble PW, Williams KL, Wright JR. The role of surfactant protein A in bleomycin-induced acute lung injury. Am J Respir Crit Care Med. 2010;181(12):1336–1344. doi:10.1164/rccm.200907-1002OC20167853
   PubMed Web of Science ®Google Scholar
• Lee JM, Yoshida M, Kim MS, et al. Involvement of Alveolar Epithelial Cell Necroptosis in Idiopathic Pulmonary Fibrosis Pathogenesis. Am J Respir Cell Mol Biol. 2018;59(2):215–224. doi:10.1165/rcmb.2017-0034OC29444413
   PubMed Web of Science ®Google Scholar
• Park SW, Lee JM, Yoshida M, et al. Involvement of RIPK3-regulated necroptosis in IPF pathogenesis. Eur Respir J. 2017;50(suppl61):OA4440. doi:10.1183/1393003.congress-2017.OA4440
   Web of Science ®Google Scholar
• Ren J, Deng Y, Xiao B, Wang G, Tao Z. Protective effects of exogenous surfactant protein A in allergic rhinitis: a mouse model. Ann Otol Rhinol Laryngol. 2013;122(4):240–246. doi:10.1177/00034894131220040523697321
   PubMed Web of Science ®Google Scholar
• Giannoni E, Sawa T, Allen L, Wiener-Kronish J, Hawgood S. Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2006;34(6):704–710. doi:10.1165/rcmb.2005-0461OC16456184
   PubMed Web of Science ®Google Scholar
• Ahn M-H, Park B-L, Lee S-H, et al. A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode. Respir Res. 2011;12(1):73. doi:10.1186/1465-9921-12-7321649933
   PubMedGoogle Scholar
• Vasakova M, Sterclova M, Matej R, et al. IL-4 polymorphisms, HRCT score and lung tissue markers in idiopathic pulmonary fibrosis. Hum Immunol. 2013;74(10):1346–1351. doi:10.1016/j.humimm.2013.07.01123911740
   PubMed Web of Science ®Google Scholar
• Kishore A, Žižková V, Kocourková L, et al. Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations. Front Immunol. 2016;7:274. doi:10.3389/fimmu.2016.0027427462317
   PubMed Web of Science ®Google Scholar
• Xin L, Jiang M, Su G, et al. The association between transforming growth factor beta1 polymorphism and susceptibility to pulmonary fibrosis: A meta-analysis (MOOSE compliant). Medicine. 2018;97(37):e11876–e11876. doi:10.1097/MD.000000000001187630212926
   PubMed Web of Science ®Google Scholar
• Mushiroda T, Wattanapokayakit S, Takahashi A, et al. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet. 2008;45(10):654–656.18835860
   PubMed Web of Science ®Google Scholar
• Korthagen NM, van Moorsel CHM, Barlo NP, Kazemier KM, Ruven HJT, Grutters JC. Association between variations in cell cycle genes and idiopathic pulmonary fibrosis. PLoS One. 2012;7(1):e30442–e30442. doi:10.1371/journal.pone.003044222291954
   PubMed Web of Science ®Google Scholar
• Nogee LM, Dunbar AE 3rd, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344(8):573–579. doi:10.1056/nejm20010222344080511207353
   PubMed Web of Science ®Google Scholar
• Lawson WE, Grant SW, Ambrosini V, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59(11):977–980. doi:10.1136/thx.2004.02633615516475
   PubMed Web of Science ®Google Scholar
• Campo I, Zorzetto M, Mariani F, et al. A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant. Respir Res. 2014;15(1):43. doi:10.1186/1465-9921-15-4324730976
   PubMedGoogle Scholar
• Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356(13):1317–1326. doi:10.1056/NEJMoa06615717392301
   PubMed Web of Science ®Google Scholar
• Alder JK, Chen JJL, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 2008;105(35):13051–13056. doi:10.1073/pnas.080428010518753630
   PubMed Web of Science ®Google Scholar
• Tsakiri KD, Cronkhite JT, Kuan PJ, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104(18):7552–7557. doi:10.1073/pnas.070100910417460043
   PubMed Web of Science ®Google Scholar
• Alder JK, Stanley SE, Wagner CL, Hamilton M, Hanumanthu VS, Armanios M. Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis. Chest. 2015;147(5):1361–1368. doi:10.1378/chest.14-194725539146
   PubMed Web of Science ®Google Scholar
• Kropski JA, Mitchell DB, Markin C, et al. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest. 2014;146(1):e1–e7. doi:10.1378/chest.13-222424504062
   PubMed Web of Science ®Google Scholar
• Cogan JD, Kropski JA, Zhao M, et al. Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med. 2015;191(6):646–655. doi:10.1164/rccm.201408-1510OC25607374
   PubMed Web of Science ®Google Scholar
• Kannengiesser C, Borie R, Ménard C, et al. Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis. Eur Respir J. 2015;46(2):474–485. doi:10.1183/09031936.0004011526022962
   PubMed Web of Science ®Google Scholar
• Stuart BD, Choi J, Zaidi S, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47(5):512–517. doi:10.1038/ng.327825848748
   PubMed Web of Science ®Google Scholar