Macrophage and innate lymphoid cell interplay in the genesis of fibrosis

Frontiers in Immunology

Volumn 6, Issue NOV, 2015, Pages

  Hams, Emily ^a   Bermingham, Rachel ^a   Fallon, Padraic G ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

Epithelial derived cytokines; Fibrosis; Innate lymphoid cells; Macrophages; Th2 cells

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; AROMATIC HYDROCARBON RECEPTOR; CONNECTIVE TISSUE GROWTH FACTOR; CXCL1 CHEMOKINE; GAMMA INTERFERON; IBUPROFEN; INHIBITOR OF DIFFERENTIATION 2; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 25; INTERLEUKIN 33; INTERLEUKIN 4; INTERLEUKIN 5; PLATELET DERIVED GROWTH FACTOR; RETINOID RELATED ORPHAN RECEPTOR ALPHA; RETINOID RELATED ORPHAN RECEPTOR GAMMA; THYMIC STROMAL LYMPHOPOIETIN; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR RUNX3; TRANSCRIPTION FACTOR T BET; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; UNINDEXED DRUG;

ADAPTIVE IMMUNITY; ANGIOGENESIS; APOPTOSIS; EPITHELIAL MESENCHYMAL TRANSITION; EPITHELIUM; FIBROSIS; INFLAMMATION; INNATE IMMUNITY; KERATINOCYTE; LYMPHOID CELL; LYMPHOID PROGENITOR CELL; MACROPHAGE; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; WOUND HEALING;

EID: 84949554279     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00597     Document Type: Review

References (117)

1. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med (2012) 18:1028-40. doi: 10.1038/nm.2807.
2. Pellicoro A, Ramachandran P, Iredale JP, Fallowfield JA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol (2014) 14:181-94. doi:10.1038/nri3623.
3. Papiris SA, Manali ED, Kolilekas L, Triantafillidou C, Tsangaris I, Kagouridis K. Steroids in idiopathic pulmonary fibrosis acute exacerbation: defenders or killers? Am J Respir Crit Care Med (2012) 185:587-8. doi:10.1164/ajrccm.185.5.587.
4. Mogayzel PJ Jr, Naureckas ET, Robinson KA, Mueller G, Hadjiliadis D, Hoag JB, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med (2013) 187:680-9. doi:10.1164/rccm.201207-1160OE.
5. Cantin AM, Hartl D, Konstan MW, Chmiel JF. Inflammation in cystic fibrosis lung disease: pathogenesis and therapy. J Cyst Fibros (2015) 14:419-30. doi:10.1016/j.jcf.2015.03.003.
6. Camelo A, Dunmore R, Sleeman MA, Clarke DL. The epithelium in idiopathic pulmonary fibrosis: breaking the barrier. Front Pharmacol (2014) 4:173. doi:10.3389/fphar.2013.00173.
7. Ellson CD, Dunmore R, Hogaboam CM, Sleeman MA, Murray LA. Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol (2014) 51:163-8. doi:10.1165/rcmb.2013-0366TR.
8. Kubes P, Mehal WZ. Sterile inflammation in the liver. Gastroenterology (2012) 143:1158-72. doi:10.1053/j.gastro.2012.09.008.
9. Artlett CM. Inflammasomes in wound healing and fibrosis. J Pathol (2013) 229:157-67. doi:10.1002/path.4116.
10. Gasse P, Riteau N, Charron S, Girre S, Fick L, Petrilli V, et al. Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis. Am J Respir Crit Care Med (2009) 179:903-13. doi:10.1164/rccm.200808-1274OC.
11. Marchiando AM, Graham WV, Turner JR. Epithelial barriers in homeostasis and disease. Annu Rev Pathol (2010) 5:119-44. doi:10.1146/annurev.pathol.4.110807.092135.
12. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol (2014) 15:178-96. doi:10.1038/nrm3758.
13. Gressner OA, Rizk MS, Kovalenko E, Weiskirchen R, Gressner AM. Changing the pathogenetic roadmap of liver fibrosis? Where did it start; where will it go? J Gastroenterol Hepatol (2008) 23:1024-35. doi:10.1111/j.1440-1746.2008.05345.x.
14. Phanish MK, Winn SK, Dockrell ME. Connective tissue growth factor-(CTGF, CCN2)-a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol (2010) 114:e83-92. doi:10.1159/000262316.
15. Rosenbloom J, Mendoza FA, Jimenez SA. Strategies for anti-fibrotic therapies. Biochim Biophys Acta (2013) 1832:1088-103. doi:10.1016/j.bbadis.2012.12.007.
16. Selman M, Pardo A. Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers. Proc Am Thorac Soc (2006) 3:364-72. doi:10.1513/pats.200601-003TK.
17. Leslie KO. Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis. Arch Pathol Lab Med (2012) 136:591-600. doi:10.5858/arpa.2011-0511-OA.
18. Divekar R, Kita H. Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation. Curr Opin Allergy Clin Immunol (2015) 15:98-103. doi:10.1097/ACI.0000000000000133.
19. Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban JF Jr, Tocker JE, et al. IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature (2010) 464:1362-6. doi:10.1038/nature08901.
20. Corrigan CJ, Wang W, Meng Q, Fang C, Eid G, Caballero MR, et al. Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses. J Allergy Clin Immunol (2011) 128:116-24. doi:10.1016/j.jaci.2011.03.043.
21. Hams E, Armstrong ME, Barlow JL, Saunders SP, Schwartz C, Cooke G, et al. IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proc Natl Acad Sci U S A (2014) 111:367-72. doi:10.1073/pnas.1315854111.
22. Yao X, Wang W, Li Y, Lv Z, Guo R, Corrigan CJ, et al. Characteristics of IL-25 and allergen-induced airway fibrosis in a murine model of asthma. Respirology (2015) 20:730-8. doi:10.1111/resp.12546.
23. Lonati PA, Brembilla NC, Montanari E, Fontao L, Gabrielli A, Vettori S, et al. High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis. PLoS One (2014) 9:e105008. doi:10.1371/journal.pone.0105008.
24. Lloyd CM, Saglani S. Epithelial cytokines and pulmonary allergic inflammation. Curr Opin Immunol (2015) 34:52-8. doi:10.1016/j.coi.2015.02.001.
25. Beale J, Jayaraman A, Jackson DJ, Macintyre JD, Edwards MR, Walton RP, et al. Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation. Sci Transl Med (2014) 6:256ra134. doi:10.1126/scitranslmed.3009124.
26. Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, et al. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol (2007) 120:1324-31. doi:10.1016/j.jaci.2007.07.051.
27. Gregory LG, Jones CP, Walker SA, Sawant D, Gowers KH, Campbell GA, et al. IL-25 drives remodelling in allergic airways disease induced by house dust mite. Thorax (2013) 68:82-90. doi:10.1136/thoraxjnl-2012-202003.
28. Liu J, Zhou X, Zhan Z, Meng Q, Han Y, Shi Q, et al. IL-25 regulates the polarization of macrophages and attenuates obliterative bronchiolitis in murine trachea transplantation models. Int Immunopharmacol (2015) 25:383-92. doi:10.1016/j.intimp.2015.02.003.
29. Afonina IS, Muller C, Martin SJ, Beyaert R. Proteolytic processing of interleukin-1 family cytokines: variations on a common theme. Immunity (2015) 42:991-1004. doi:10.1016/j.immuni.2015.06.003.
30. Yanaba K, Yoshizaki A, Asano Y, Kadono T, Sato S. Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. Clin Rheumatol (2011) 30:825-30. doi:10.1007/s10067-011-1686-5.
31. Hamzaoui A, Berraies A, Kaabachi W, Haifa M, Ammar J, Kamel H. Induced sputum levels of IL-33 and soluble ST2 in young asthmatic children. J Asthma (2013) 50:803-9. doi:10.3109/02770903.2013.816317.
32. Guo Z, Wu J, Zhao J, Liu F, Chen Y, Bi L, et al. IL-33 promotes airway remodeling and is a marker of asthma disease severity. J Asthma (2014) 51:863-9. doi:10.3109/02770903.2014.921196.
33. Marvie P, Lisbonne M, L'Helgoualc'h A, Rauch M, Turlin B, Preisser L, et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med (2010) 14:1726-39. doi:10.1111/j.1582-4934.2009.00801.x.
34. Luzina IG, Kopach P, Lockatell V, Kang PH, Nagarsekar A, Burke AP, et al. Interleukin-33 potentiates bleomycin-induced lung injury. Am J Respir Cell Mol Biol (2013) 49:999-1008. doi:10.1165/rcmb.2013-0093OC.
35. Li D, Guabiraba R, Besnard AG, Komai-Koma M, Jabir MS, Zhang L, et al. IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice. J Allergy Clin Immunol (2014) 134:1422-1432e11. doi:10.1016/j.jaci.2014.05.011.
36. Masterson JC, Capocelli KE, Hosford L, Biette K, McNamee EN, de Zoeten EF, et al. Eosinophils and IL-33 perpetuate chronic inflammation and fibrosis in a pediatric population with stricturing Crohn's ileitis. Inflamm Bowel Dis (2015) 21(10):2429-40.
37. Sedhom MA, Pichery M, Murdoch JR, Foligne B, Ortega N, Normand S, et al. Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice. Gut (2013) 62:1714-23. doi:10.1136/gutjnl-2011-301785.
38. Cohen ES, Scott IC, Majithiya JB, Rapley L, Kemp BP, England E, et al. Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. Nat Commun (2015) 6:8327. doi:10.1038/ncomms9327.
39. McHedlidze T, Waldner M, Zopf S, Walker J, Rankin AL, Schuchmann M, et al. Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis. Immunity (2013) 39:357-71. doi:10.1016/j.immuni.2013.07.018.
40. Li J, Razumilava N, Gores GJ, Walters S, Mizuochi T, Mourya R, et al. Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation. J Clin Invest (2014) 124:3241-51. doi:10.1172/JCI73742.
41. Ying S, O'Connor B, RatoffJ, Meng Q, Fang C, Cousins D, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol (2008) 181:2790-8. doi:10.4049/jimmunol.181.4.2790.
42. Wu J, Liu F, Zhao J, Wei Y, Lv J, Dong F, et al. Thymic stromal lymphopoietin promotes asthmatic airway remodelling in human lung fibroblast cells through STAT3 signalling pathway. Cell Biochem Funct (2013) 31:496-503. doi:10.1002/cbf.2926.
43. Christmann RB, Mathes A, Affandi AJ, Padilla C, Nazari B, Bujor AM, et al. Thymic stromal lymphopoietin is up-regulated in the skin of patients with systemic sclerosis and induces profibrotic genes and intracellular signaling that overlap with those induced by interleukin-13 and transforming growth factor beta. Arthritis Rheum (2013) 65:1335-46. doi:10.1002/art.37859.
44. Herro R, Da Silva Antunes R, Aguilera AR, Tamada K, Croft M. Tumor necrosis factor superfamily 14 (LIGHT) controls thymic stromal lymphopoietin to drive pulmonary fibrosis. J Allergy Clin Immunol (2015) 136(3):757-68. doi:10.1016/j.jaci.2014.12.1936.
45. Herro R, Antunes Rda S, Aguilera AR, Tamada K, Croft M. The tumor necrosis factor superfamily molecule LIGHT promotes keratinocyte activity and skin fibrosis. J Invest Dermatol (2015) 135:2109-18. doi:10.1038/jid.2015.110.
46. Van Dyken SJ, Mohapatra A, Nussbaum JC, Molofsky AB, Thornton EE, Ziegler SF, et al. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and gammadelta T cells. Immunity (2014) 40:414-24. doi:10.1016/j.immuni.2014.02.003.
47. Klose CS, Flach M, Mohle L, Rogell L, Hoyler T, Ebert K, et al. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell (2014) 157:340-56. doi:10.1016/j.cell.2014.03.030.
48. Geiger TL, Abt MC, Gasteiger G, Firth MA, O'Connor MH, Geary CD, et al. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med (2014) 211:1723-31. doi:10.1084/jem.20140212.
49. Constantinides MG, McDonald BD, Verhoef PA, Bendelac A. A committed precursor to innate lymphoid cells. Nature (2014) 508:397-401. doi:10.1038/nature13047.
50. Xu W, Domingues RG, Fonseca-Pereira D, Ferreira M, Ribeiro H, Lopez-Lastra S, et al. NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Cell Rep (2015) 10:2043-54. doi:10.1016/j.celrep.2015.02.057.
51. Seehus CR, Aliahmad P, de la Torre B, Iliev ID, Spurka L, Funari VA, et al. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor. Nat Immunol (2015) 16:599-608. doi:10.1038/ni.3168.
52. Eberl G, Colonna M, Di Santo JP, McKenzie AN. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science (2015) 348:aaa6566. doi:10.1126/science.aaa6566.
53. Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med (2015) 21:698-708. doi:10.1038/nm.3892.
54. Yang Q, Li F, Harly C, Xing S, Ye L, Xia X, et al. TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow. Nat Immunol (2015) 16(10):1044-50. doi:10.1038/ni.3248.
55. Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, et al. Transcription factor RORalpha is critical for nuocyte development. Nat Immunol (2012) 13:229-36. doi:10.1038/ni.2208.
56. Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I, McNagny KM, et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity (2014) 40:425-35. doi:10.1016/j.immuni.2014.01.011.
57. Walker JA, Oliphant CJ, Englezakis A, Yu Y, Clare S, Rodewald HR, et al. Bcl11b is essential for group 2 innate lymphoid cell development. J Exp Med (2015) 212:875-82. doi:10.1084/jem.20142224.
58. Yu Y, Wang C, Clare S, Wang J, Lee SC, Brandt C, et al. The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development. J Exp Med (2015) 212:865-74. doi:10.1084/jem.20142318.
59. Qiu J, Heller JJ, Guo X, Chen ZM, Fish K, Fu YX, et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity (2012) 36:92-104. doi:10.1016/j.immuni.2011.11.011.
60. Bernink JH, Krabbendam L, Germar K, de Jong E, Gronke K, Kofoed-Nielsen M, et al. Interleukin-12 and-23 control plasticity of CD127(+) group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity (2015) 43:146-60. doi:10.1016/j.immuni.2015.06.019.
61. Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U, et al. IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol (2015) 16:161-9. doi:10.1038/ni.3078.
62. Califano D, Cho JJ, Uddin MN, Lorentsen KJ, Yang Q, Bhandoola A, et al. Transcription factor Bcl11b controls identity and function of mature type 2 innate lymphoid cells. Immunity (2015) 43(2):354-68. doi:10.1016/j.immuni.2015.07.005.
63. Villanova F, Flutter B, Tosi I, Grys K, Sreeneebus H, Perera GK, et al. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J Invest Dermatol (2014) 134:984-91. doi:10.1038/jid.2013.477.
64. Kim HY, Lee HJ, Chang YJ, Pichavant M, Shore SA, Fitzgerald KA, et al. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med (2014) 20:54-61. doi:10.1038/nm.3423.
65. Wilson MS, Madala SK, Ramalingam TR, Gochuico BR, Rosas IO, Cheever AW, et al. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J Exp Med (2010) 207:535-52. doi:10.1084/jem.20092121.
66. Brodlie M, McKean MC, Johnson GE, Anderson AE, Hilkens CM, Fisher AJ, et al. Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease. Eur Respir J (2011) 37:1378-85. doi:10.1183/09031936.00067110.
67. Choy DF, Hart KM, Borthwick LA, Shikotra A, Nagarkar DR, Siddiqui S, et al. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med (2015) 7:301ra129. doi:10.1126/scitranslmed.aab3142.
68. Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, et al. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med (2006) 203:1105-16. doi:10.1084/jem.20051615.
69. Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature (2010) 464:1367-70. doi:10.1038/nature08900.
70. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol (2011) 12:1045-54. doi:10.1031/ni.2131.
71. Turner JE, Morrison PJ, Wilhelm C, Wilson M, Ahlfors H, Renauld JC, et al. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J Exp Med (2013) 210:2951-65. doi:10.1084/jem.20130071.
72. Hoyler T, Klose CS, Souabni A, Turqueti-Neves A, Pfeifer D, Rawlins EL, et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity (2012) 37:634-48. doi:10.1016/j.immuni.2012.06.020.
73. Barlow JL, McKenzie AN. Type-2 innate lymphoid cells in human allergic disease. Curr Opin Allergy Clin Immunol (2014) 14:397-403. doi:10.1097/ACI.0000000000000090.
74. McKenzie AN. Type-2 innate lymphoid cells in asthma and allergy. Ann Am Thorac Soc (2014) 11(Suppl 5):S263-70. doi:10.1513/AnnalsATS.201403-097AW.
75. Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, et al. Human IL-25-and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol (2011) 12:1055-62. doi:10.1038/ni.2104.
76. Salimi M, Barlow JL, Saunders SP, Xue L, Gutowska-Owsiak D, Wang X, et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med (2013) 210:2939-50. doi:10.1084/jem.20130351.
77. Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol (2014) 134:671-678e4. doi:10.1016/j.jaci.2014.06.024.
78. Saunders SP, Moran T, Floudas A, Wurlod F, Kaszlikowska A, Salimi M, et al. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. J Allergy Clin Immunol (2015). doi:10.1016/j.jaci.2015.06.045.
79. Imai Y, Yasuda K, Sakaguchi Y, Haneda T, Mizutani H, Yoshimoto T, et al. Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice. Proc Natl Acad Sci U S A (2013) 110:13921-6. doi:10.1073/pnas.1307321110.
80. Oliphant CJ, Hwang YY, Walker JA, Salimi M, Wong SH, Brewer JM, et al. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity (2014) 41:283-95. doi:10.1016/j.immuni.2014.06.016.
81. Mirchandani AS, Besnard AG, Yip E, Scott C, Bain CC, Cerovic V, et al. Type 2 innate lymphoid cells drive CD4+ Th2 cell responses. J Immunol (2014) 192:2442-8. doi:10.4049/jimmunol.1300974.
82. Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol (1991) 37:823-9.
83. Bailey JR, Bland PW, Tarlton JF, Peters I, Moorghen M, Sylvester PA, et al. IL-13 promotes collagen accumulation in Crohn's disease fibrosis by down-regulation of fibroblast MMP synthesis: a role for innate lymphoid cells? PLoS One (2012) 7:e52332. doi:10.1371/journal.pone.0052332.
84. Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest (1999) 103:779-88. doi:10.1172/JCI5909.
85. Gharaee-Kermani M, Phan SH. Lung interleukin-5 expression in murine bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol (1997) 16:438-47. doi:10.1165/ajrcmb.16.4.9115755.
86. Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest (1999) 104:777-85. doi:10.1172/JCI7325.
87. Fallon PG, Richardson EJ, McKenzie GJ, McKenzie AN. Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J Immunol (2000) 164:2585-91. doi:10.4049/jimmunol.164.5.2585.
88. Kumar RK, Herbert C, Yang M, Koskinen AM, McKenzie AN, Foster PS. Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma. Clin Exp Allergy (2002) 32:1104-11. doi:10.1046/j.1365-2222.2002.01420.x.
89. Kolodsick JE, Toews GB, Jakubzick C, Hogaboam C, Moore TA, McKenzie A, et al. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J Immunol (2004) 172:4068-76. doi:10.4049/jimmunol.172.7.4068.
90. Fallon PG, Jolin HE, Smith P, Emson CL, Townsend MJ, Fallon R, et al. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity (2002) 17:7-17. doi:10.1016/S1074-7613(02)00332-1.
91. De Boever EH, Ashman C, Cahn AP, Locantore NW, Overend P, Pouliquen IJ, et al. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J Allergy Clin Immunol (2014) 133:989-96. doi:10.1016/j.jaci.2014.01.002.
92. Chiaramonte MG, Mentink-Kane M, Jacobson BA, Cheever AW, Whitters MJ, Goad ME, et al. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med (2003) 197:687-701. doi:10.1084/jem.20020903.
93. Doucet C, Brouty-Boye D, Pottin-Clemenceau C, Canonica GW, Jasmin C, Azzarone B. Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J Clin Invest (1998) 101:2129-39. doi:10.1172/JCI741.
94. Saito A, Okazaki H, Sugawara I, Yamamoto K, Takizawa H. Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro. Int Arch Allergy Immunol (2003) 132:168-76. doi:10.1159/000073718.
95. Hepworth MR, Monticelli LA, Fung TC, Ziegler CG, Grunberg S, Sinha R, et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature (2013) 498:113-7. doi:10.1038/nature12240.
96. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol (2011) 11:723-37. doi:10.1038/nri3073.
97. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature (2013) 496:445-55. doi:10.1038/nature12034.
98. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity (2014) 41:14-20. doi:10.1016/j.immuni.2014.06.008.
99. Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol (2015) 15:271-82. doi:10.1038/nri3831.
100. Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science (2011) 332:1284-8. doi:10.1126/science.1204351.
101. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest (2005) 115:56-65. doi:10.1172/JCI200522675.
102. Borthwick LA, Barron L, Hart KM, Vannella KM, Thompson RW, Oland S, et al. Macrophages are critical to the maintenance of IL-13-dependent lung inflammation and fibrosis. Mucosal Immunol (2015). doi:10.1038/mi.2015.34.
103. Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol (2014) 60:1090-6. doi:10.1016/j.jhep.2013.12.025.
104. El Kasmi KC, Stenmark KR. Contribution of metabolic reprogramming to macrophage plasticity and function. Semin Immunol (2015). doi:10.1016/j.smim.2015.09.001.
105. Kelly B, O'Neill LA. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res (2015) 25:771-84. doi:10.1038/cr.2015.68.
106. Zhu L, Zhao Q, Yang T, Ding W, Zhao Y. Cellular metabolism and macrophage functional polarization. Int Rev Immunol (2015) 34:82-100. doi:10.3109/08830185.2014.969421.
107. Galvan-Pena S, O'Neill LA. Metabolic reprograming in macrophage polarization. Front Immunol (2014) 5:420. doi:10.3389/fimmu.2014.00420.
108. Vannella KM, Barron L, Borthwick LA, Kindrachuk KN, Narasimhan PB, Hart KM, et al. Incomplete deletion of IL-4Ralpha by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis. PLoS Pathog (2014) 10:e1004372. doi:10.1371/journal.ppat.1004372.
109. Thompson RW, Pesce JT, Ramalingam T, Wilson MS, White S, Cheever AW, et al. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathog (2008) 4:e1000023. doi:10.1371/journal.ppat.1000023.
110. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog (2009) 5:e1000371. doi:10.1371/journal.ppat.1000371.
111. Titos E, Rius B, Gonzalez-Periz A, Lopez-Vicario C, Moran-Salvador E, Martinez-Clemente M, et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol (2011) 187:5408-18. doi:10.4049/jimmunol.1100225.
112. Schif-Zuck S, Gross N, Assi S, Rostoker R, Serhan CN, Ariel A. Saturated-efferocytosis generates pro-resolving CD11b low macrophages: modulation by resolvins and glucocorticoids. Eur J Immunol (2011) 41:366-79. doi:10.1002/eji.201040801.
113. Han H, Headley MB, Xu W, Comeau MR, Zhou B, Ziegler SF. Thymic stromal lymphopoietin amplifies the differentiation of alternatively activated macrophages. J Immunol (2013) 190:904-12. doi:10.4049/jimmunol.1201808.
114. Huang Q, Niu Z, Tan J, Yang J, Liu Y, Ma H, et al. IL-25 elicits innate lymphoid cells and multipotent progenitor type 2 cells that reduce renal ischemic/reperfusion injury. J Am Soc Nephrol (2015) 26(9):2199-211. doi:10.1681/ASN.2014050479.
115. Bouchery T, Kyle R, Camberis M, Shepherd A, Filbey K, Smith A, et al. ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms. Nat Commun (2015) 6:6970. doi:10.1038/ncomms7970.
116. Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med (2013) 210:535-49. doi:10.1084/jem.20121964.
117. Iredale JP, Bataller R. Identifying molecular factors that contribute to resolution of liver fibrosis. Gastroenterology (2014) 146:1160-4. doi:10.1053/j.gastro.2014.03.019.