Review Article
 

Role of Innate Lymphoid Cells in Lung Disease

Abstract

Innate lymphoid cells (ILCs) are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th)1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages.Three types of ILCs (ILC1, 2&3) have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK) cells and interferon (IFN)-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated in mucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis.There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD). Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases.In this review we will focus on the role of ILC2 cells and consider their origin, function, location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD.

1. Monticelli LA, Sonnenberg GF, Artis D. Innate lymphoid cells: critical regulators of allergic inflammation and tissue repair in the lung. Curr Opin Immunol 2012; 24(3):284–9.

2. Spits H, Cupedo T. Innate lymphoid cells: emerging insights indevelopment, lineage relationships, and function. Annu Rev Immunol 2012; 30:647-75-.

3. Spits H, Di Santo JP. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol 2011; 12(1):21-7.

4. Saenz SA, Noti M, Artis D. Innate immune cell populations function as initiators and effectors in Th2 cytokine responses. Trends Immunol 2010; 31(11):407-13.

5. Spits H and Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol 2012;30:647–75.

6. Vivier E, Spits H, Cupedo T. Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair. Nat Rev Immunol 2009;9(4):229–34.

7. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2008; 457(7230):722–5.

8. Crellin NK, Trifari S, Kaplan CD, Satoh-Takayama N, Di Santo JP, Spits H. Regulation of cytokine secretion in human CD127+ LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity 2010;33(5):752–64.

9. Takatori H, Kanno Y, Watford WT, TatoCM,Weiss G, Weiss G, Ivanov II, et al. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 2009; 206(1):35–41.

10. Guo L, Junttila IS, Paul WE. Cytokine-induced cytokine production by conventional and innate lymphoid cells. Trends Immunol 2012; 33(12):598-606.

11. Kelly KA, Scollay R. Seeding of neonatal lymph nodes by T cells and identification of a novel population of CD3−CD4+ cells. Eur J Immunol 1992; 22(2):329–34.

12. Mebius RE, Rennert P, Weissman IL. Developing lymph nodes collect CD4+CD3−LTβ+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 1997; 7(4):493–504.

13. Cherrier M, Eberl G. The development of LTi cells.Curr Opin Immunol 2012; 24(2):178–83.

14. Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, et al. Human fetal lymphoid tissueinducercells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 2009; 10(1):66–74.

15. Randall TD, Carragher DM, Rangel-Moreno J.Development of secondary lymphoid organs. Annu Rev Immunol 2008; 26:627–50.

16. van de Pavert SA, Mebius RE. New insights into the development of lymphoid tissues. Nat Rev Immunol 2010; 10(9):664–74.

17. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR. An essential function for the nuclear receptor RORγ(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 2004; 5(1):64–73.

18. Kurebayashi S, Ueda E, Sakaue M, Patel DD, Medvedev A, Zhang F, et al. Retinoid-related orphan receptor γ(ROR γ) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Proc Natl Acad Sci USA 2000;97(18):10132–7.

19. Sun Z, Unutmaz D, Zou YR, SunshineMJ, Pierani A, Brenner-Morton S, et al. Requirement for RORγinthymocyte survival and lymphoid organ development. Science 2000; 288(5475):2369–73.

20. Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, et al. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol 2012; 13(2):144–51.

21. Hirose T, Smith RJ, Jetten AM. RORγ: The third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. Biochem Biophys Res Commun 1994; 205(3):1976–83.

22. Villey I, deChasseval R, de Villartay JP. RORγT, a thymus-specific isoform of the orphan nuclear receptor RORγ/TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter. Eur J Immunol 1999; 29(12):4072–80.

23. He YW, Beers C, Deftos ML, Ojala EW, Forbush KA, Bevan MJ. Down-regulation of the orphan nuclear receptor RORγt is essential for T lymphocyte maturation. J Immunol 2000; 164(11):5668–74.

24. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126(6):1121–33.

25. Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S, Maki K, et al. IL-7 receptor α+ CD3− cells in the embryonic intestine induces the organizing center of Peyer’s patches. Int Immunol 1999;11(5):643–55.

26. van de Pavert SA, Olivier BJ, Goverse G, Vondenhoff MF, Greuter M, Beke P, et al. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol 2009; 10(11):1193–9.

27. Finke D. Fate and function of lymphoid tissue inducer cells. Curr Opin Immunol 2005; 17(2):144–50.

28. Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, et al. Human IL-25-responsive and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 2011; 12(11):1055-62.

29. 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(7293):1367-70.

30. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, , Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 2010; 463(7280):540–4.

31. Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE, et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol 2011; 12(7):631-8.

32. Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci USA 2010; 107(25):11489-94.

33. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lungtissue homeostasis after infection with influenza virus. Nat Immunol 2011; 12(11):1045-54.

34. Ikutani M, Yanagibashi T, Ogasawara M, Tsuneyama K, Yamamoto S, Hattori Y, et al. Identification of innate IL-5-producing cellsand their role in lung eosinophil regulation and antitumor immunity. J Immunol 2012; 188(2):703–13.

35. Bartemes KR, Iijima K, Kobayashi T, Kephart GM,McKenzie AN, Kita H. IL-33-responsive lineage-

CD25+CD44hi lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs. J Immunol 2012; 188(3):1503–13.

36. 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(3):229-36.

37. Liang HE, Reinhardt RL, Bando JK, Sullivan BM, Ho IC, Locksley RM. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat Immunol 2012; 13(1):58–66.

38. Yang Q, Saenz SA, Zlotoff DA, Artis D, Bhandoola A. Cutting edge: natural helper cells derive fromlymphoid progenitors. J Immunol 2011; 187(11):5505–9.

39. Halim TY, Krauss RH, Sun AC, Takei F. Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity 2012; 36(3):451-63.

40. Scanlon ST, McKenzie AN. Type 2 innate lymphoid cells: new players in asthma and allergy. Curr Opin Immunol 2012; 24(6):707–12.

41. Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, et al. The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3− cells, as well as macrophages. J Immunol 2001; 166(11):6593–601.

42. Cella M, Otero K, Colonna M. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. Proc Natl Acad Sci USA 2010; 107(24):10961–6.

43. Colonna M. Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. Immunity 2009; 31(1):15–23.

44. Satoh-Takayama N, Lesjean-Pottier S, Vieira P, Sawa S, Eberl G, Vosshenrich CA, et al. IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J Exp Med 2010; 207(2):273–80.

45. Vonarbourg C, Mortha A, Bui VL, Hernandez PP, Kiss EA, Hoyler T, et al. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt+ innate lymphocytes. Immunity 2010; 33(5):736–51.

46. Freud AG, Yokohama A, Becknell B, Lee MT, Mao HC, Ferketich AK, et al. Evidence for discrete stages of human natural killer cell differentiation in vivo. J Exp Med 2006; 203(4):1033–43.

47. Hughes T, Becknell B, McCloryS, Briercheck E, Freud AG, Zhang X, et al. Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22. Blood 2009; 113(17):4008–10.

48. Hughes T, Becknell B, Freud AG, McClory S, Briercheck E, Yu J, et al. Interleukin-1β selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. Immunity 2010; 32(6):803–14.

49. Crellin NK, TrifariS, Kaplan CD, Cupedo T, Spits H. Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. J. Exp. Med 2010; 207(2):281–90.

50. Barlow JL, Bellosi A, Hardman CS, Drynan LF, Wong SH, Cruickshank JP, et al. Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J Allergy Clin Immunol 2012; 129(1):191-8.

51. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S,et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2- associated pathologies in vivo. Immunity 2001;15(6):985–95.

52. Walker JA, McKenzie A. Innate lymphoid cells in the airways. Eur J Immunol 2012; 42(6):1368–74.

53. 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(4):1105–16.

54. Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 2002;169(1):443–53.

55. Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, et al. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 2009;10(1):83–91.

56. Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 2008; 29(6):958–70.

57. Geremia A, Arancibia-Carcamo CV, FlemingMP, Rust N, Singh B, Mortensen NJ, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med 2011; 208(6):1127–33.

58. Cella M, Otero K, Colonna M. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. Proc Natl Acad Sci U S A 2010;107(24):10961–6.

59. Reynders A, Yessaad N, Vu Manh TP, Dalod M, Fenis A, Aubry C, et al. Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt− lymphoid cells. EMBO J 2011; 30(14):2934–47.

60. Luci C, Reynders A, Ivanov II, Cognet C, Chiche L, Chasson L, et al. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin. Nat Immunol 2009; 10(1):75–82.

61. Di Meglio P, Villanova F, Napolitano L, Tosi I,Terranova Barberio M, Mak RK, et al. The IL23R A/Gln381 Allele Promotes IL-23 Unresponsiveness in Human Memory T-Helper 17 Cells and Impairs Th17 Responses in Psoriasis Patients. J Invest Dermatol 2013; 133(10):2381-9.

62. Kim S, Han S, Withers DR, Gaspal F, Bae J, Baik S, et al. CD117+ CD3− CD56− OX40Lhigh cellsexpress IL- 22 and display an LTi phenotype in human secondary lymphoid tissues. Eur J Immunol 2011; 41(6):1563–72.

63. Eberl G, Littman DR. Thymic origin of intestinal αβTcells revealed by fatemappingofRORγt+ cells. Science 2004; 305(5891):248–51.

64. TsujiM, Suzuki K, Kitamura H,MaruyaM, Kinoshita K, et al. Requirement for lymphoid tissueinducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 2008; 29:261–71.

65. Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K, Nariuchi H, et al. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c- kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop. J Exp Med 1996; 184(4):1449–59.

66. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of themouse small intestine. J Immunol 2002; 168(1):57–64.

67. Scandella E, Bolinger B, Lattmann E, Miller S, Favre S, Littman DR, et al. Restoration of lymphoid organ integrity through the interaction of lymphoid tissue- inducer cells with stroma of the T cell zone. Nat Immunol 2008; 9(6):667–75.

68. Buonocore S, Ahern PP, Uhlig HH, Ivanov II, Littman DR, Maloy KJ, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 2010; 464(7293):1371–5.

69. Sawa S, Lochner M, Satoh-Takayama N, Dulauroy S, Berard M, Kleinschek M, et al. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol 2011; 12(4):320–6.

70. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004; 21(2):241–54.

71. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29:71–109.

72. Sonnenberg GF, Monticelli LA, Elloso MM, Fouser LA, Artis D. CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 2010; 34(1):122–34.

73. Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 2010; 328(5979):749–52.

74. Eisenring M, vom Berg J, Kristiansen G, Saller E, Becher B. IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat Immunol 2010; 11(11):1030–8.

75. Heath WR, Carbone FR. The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol 2013; 14(10):978-85.

76. Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK. Visualization of specific Band T lymphocyte interactions in the lymph node. Science 1998; 281(5373):96–9.

77. Lane PJ, Gaspal FM, Kim MY. Two sides of a cellular coin: CD4+CD3− cells regulate emoryresponses and lymph-node organization. Nat Rev Immunol 2005;5(8):655–60.

78. Liu YJ, Zhang J, Lane PJ, Chan EY, MacLennan IC.Sites of specific B cell activation in primaryand secondary responses toTcell-dependent andTcell- independent antigens. Eur J Immunol 1991;21(2):2951–62.

79. Kim MY, Anderson G, White A, Jenkinson E, Arlt W, et al. OX40 ligand and CD30 ligand are expressed on adult but not neonatal CD4+CD3− inducer cells: evidence that IL-7 signals regulate CD30 ligand but not OX40 ligand expression. J Immunol 2005;174(11):6686–91.

80. Kim MY, Toellner KM, White A, McConnell FM, Gaspal FM, Parnell SM, et al. Neonatal and adult CD4+ CD3− cells share similar gene expression profile, and neonatal cells up-regulateOX40 ligand in response to TL1A (TNFSF15). J Immunol 2006; 177(5):3074–81.

81. Kim MY, Gaspal FM, Wiggett HE, McConnell FM, Gulbranson-Judge A, Raykundalia C, et al. CD4+CD3− accessory cells costimulate primedCD4Tcells throughOX40andCD30at sites whereTcells collaborate with B cells. Immunity 2003; 18(5):643–54.

82. Gaspal FM, Kim MY, McConnell FM, Raykundalia C, Bekiaris V, Lane PJ. Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. J Immunol 2005;174(7):3891–6.

83. Withers DR, Jaensson E, Gaspal F, McConnell FM, Eksteen B, Anderson G, et al. The survival of memory CD4+ T cells within the gut lamina propria requires OX40 and CD30 signals. J Immunol 2009;183(8):5079–84.

84. Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 2013; 502(7470):245-8.

85. Koyasu S, Moro K, Tanabe M, Takeuchi T. Natural helper cells: a new player in the innate immuneresponse against helminthinfection. Adv Immunol 2010; 108:21-44.

86. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lungtissue homeostasis after infection with influenza virus. Nat Immunol 2011; 12(11):1045-54.

87. Kim HY, Chang YJ, Subramanian S, Lee HH, Albacker LA, Matangkasombut P, et al. Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. J Allergy Clin Immunol 2012; 129(1):216-27.

88. Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, et al. Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematodeinfected mice. Proc Natl Acad Sci U S A 2012; 109(9):3451–6.

89. Adachi S, Yoshida H, Honda K, Maki K, Saijo K, Ikuta K, et al. Essential role of IL 7 receptor α in the formation of Peyer’s patch anlage. Int Immunol 1998;10(1):1–6.

90. Fukushi M, Ito T, Oka T, Kitazawa T, Miyoshi- Akiyama T, Kirikae T, et al. Serial histopathological examination of the lungs of mice infected with Influenza A virus PR8 strain. PLoS ONE 2011;6(6):e21207.

91. Doherty T, Broide D. Cytokines and growth factors in airway remodeling in asthma. Curr Opin Immunol2007; 19(6):676-80.

92. Broide DH. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling. J Allergy ClinImmunol 2008; 121(3):560-70.

93. Crosby LM, Waters CM. Epithelial repair mechanisms in thelung. Am J Physiol Lung Cell Mol Physiol 2010;298(6):L715-31.

94. Licona-Limon P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013; 14(6):536-42.

95. Rock JR, Hogan BL. Epithelial progenitor cells in lungdevelopment, maintenance, repair, and disease. Annu Rev Cell Dev Biol 2011; 27:493-512.

96. Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol 2010; 11(7):577–84.

97. Voehringer D, Reese TA, Huang X, Shinkai K, Locksley RM. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 2006;203(6):1435–46.

98. Walter DM, McIntire JJ, Berry G, McKenzie AN, Donaldson DD, DeKruyff RH, et al. Critical role for IL-13 in the development of allergen-induced airway hyperreactivity. J Immunol 2001; 167(8):4668–75.

99. Cohn L, Tepper JS, Bottomly K. IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells. J Immunol 1998; 161(8):3813–6.

100. Oshikawa K, Kuroiwa K, Tago K, Iwahana H,Yanagisawa K, Ohno S, et al. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med 2001;164(2):277-81.

101. Sakashita M, Yoshimoto T, Hirota T, Harada M, Okubo K, Osawa Y, et al. Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis. Clin Exp Allergy 2008;38(12):1875-81.

102. Kamekura R, Kojima T, Takano K, Go M, Sawada N, Himi T. The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis. Clin Exp Allergy 2012; 42(2):218-28.

103. Prefontaine D, Lajoie-Kadoch S, Foley S, Audusseau S, Olivenstein R, Halayko AJ, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J Immunol 2009;183(8):5094-103.

104. Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, et al. Lipoxin A4 Regulates Natural Killer Cell and Type 2 Innate Lymphoid Cell Activation in Asthma. Sci Transl Med 2013; 5(174):174ra26. DOI: 10.1126/scitranslmed.3004812105. Fallon PG, Emson CL, Smith P, McKenzie AN. IL-13 overexpression predisposes to anaphylaxis following antigen sensitization. J Immunol 2001; 166(4):2712-6.

106. 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(6):779–88.

107. Jaradat M, Stapleton C, Tilley SL, Dixon D, Erikson CJ, McCaskill JG, et al. Modulatory role for retinoid- related orphan receptor alpha in allergen-induced lung inflammation. Am J Respir Crit Care Med 2006;174(12):1299–309.

108. Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, Lahl K, et al. An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 2011; 12(11):1071-7.

109. Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Morimoto M, Hayashi N, et al. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol 2008; 20(6):791–800.

110. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005; 23(5):479–90.

111. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009;15(4):410–6.

112. Pushparaj PN, Tay HK, H’Ng SC, Pitman N, Xu D, McKenzie A, et al. The cytokine interleukin-33 mediates anaphylactic shock. Proc Natl Acad Sci U S A2009; 106(24):9773–8.

113. Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med2007; 204(8):1837-47.

114. 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 latephase cutaneous responses. J Allergy Clin Immunol 2011; 128(1):116-24.

115. Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev Immunol 2011;11(6):375-88.

116. Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC. Protective immune mechanisms in helminth infection. Nat Rev Immunol 2007; 7(12):975-87.

117. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab Treatment in Adults with Asthma. N Engl J Med 2011;365(12):1088-98.

118. Taube C, Tertilt C, Gyülveszi G, Dehzad N, Kreymborg K, Schneeweiss K, et al. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease. PLoS One 2011; 6(7):e21799.

119. Zenewicz LA, Flavell RA. Recent advances in IL-22 biology. Int Immunol 2011; 23(3):159–63.

120. Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 2006; 203(12):2715–25.

121. Schnyder B, Lima C, Schnyder-Candrian S.Interleukin-22 is a negative regulator of the allergic response. Cytokine 2010; 50(2):220–7.

122. Givi ME, Redegeld FA, Folkerts G, Mortaz E.Dendritic cells in pathogenesis of COPD. Curr PharmDes 2012; 18(16):2329-35.

123. Mortaz E, Folkerts G, Redegeld F. Mast cells and COPD. Pulm Pharmacol Ther 2011; 24(4):367-72.

124. Yoshida T, Tuder RM. Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev 2007; 87(3):1047-82.

125. Besnard AG1, Sabat R, Dumoutier L, Renauld JC,Willart M, Lambrecht B, et al. Dual role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A. Am J Respir Crit Care Med 2011;183(9):1153–63.

126. Stockley, RA (Jun 2011) Chronic Obstructive Pulmonary Disease. In: eLS. John Wiley & Sons Ltd, Chichester.http://www.els.net.

127. Liesker JJ, Wijkstra PJ, Ten Hacken NH, Koëter GH, Postma DS, Kerstjens HA. A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD. Chest 2002; 121(2):597-608.

128. Hweshenson MB. Rhinovirus-induced exacerbations of asthma and COPD. Scientifica 2013; 2013:405876.

129. Wu CA, Puddington L, Whiteley HE, Yiamouyiannis CA, Schramm CM, Mohammadu F, et al. Murine cytomegalovirus infection alters TH1/TH2 cytokine expression, decreases airway eosinophilia, and enhances mucus productionin allergic airway disease. J Immunol 2001; 167(5):2798-807.

130. Almansa R, Sanchez-Garcia M, Herrero A, Calzada S, Roig V, Barbado J, et al. Host response cytokine signatures in viral and nonviral acute exacerbations of chronic obstructive pulmonary disease. J Interferon Cytokine Res 2011; 31(5):409-13.

131. Cayrol C, Girard JP. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci U S A 2009; 106(22):9021-6.

132. Lefrançais E, Roga S, Gautier V, Gonzalez-de-Peredo A, Monsarrat B, Girard JP, et al. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci U S A 2012;109(5):1673-8.

133. Piccioni PD, Kramps JA, Rudolphus A, Bulgheroni A, Luisetti M. Proteinase/proteinase inhibitor imbalance in sputum sol phases from patients with chronic obstructive pulmonary disease. Suggestions for a key role played by antileukoprotease. Chest 1992;102(5):1470-6.

134. Wickenden JA, Clarke MCH, Rossi AG, Rahman I, Faux SP, Donaldson K, et al. Cigarette smoke prevents apoptosis through inhibition of caspase activation and induces necrosis. Am J Respiratory Cell and Molecular Biol 2003; 29(5):562-70.

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IssueVol 14, No 4 (2015) QRcode
SectionReview Article(s)
Keywords
Cytokines IL-17 IL-22 ILCs Respiratory tract

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Marashian SM, Mortaz E, Jamaati HR, Alavi-Moghaddam M, Kiani A, Abedini A, Garssen J, M.Adcock I, Velayati AA. Role of Innate Lymphoid Cells in Lung Disease. Iran J Allergy Asthma Immunol. 2015;14(4):346-360.