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Open Access 01-07-2016 | Review Article

Type 2 innate lymphoid cells: at the cross-roads in allergic asthma

Published in: Seminars in Immunopathology | Issue 4/2016

Abstract

Allergic asthma is a chronic inflammatory disease of the lower airways that affects millions of people worldwide. Allergic asthma is a T helper 2 cell (Th2)-mediated disease, in which Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 are closely associated with the symptoms. IL-4 is needed by B cells to switch toward an IgE response, IL-5 recruits and activates eosinophils while IL-13 increases mucus production. The identification of type 2 innate lymphoid cells (ILC2), which are able to rapidly produce large amounts of IL-5 and IL-13 in response to epithelial derived cytokines, implicated a new key player besides Th2 cells. ILCs constitute a family of innate lymphocytes distinct from T and B cells. ILC2s are located in various epithelial compartments in mice and human, including the lung. The recent finding of increased numbers of ILC2s in the airways of severe asthma patients prompts further research to clarify their immunological function. Murine studies have shown that ILC2s are an early innate source of IL-5 and IL-13 after allergen exposure, which induce airway eosinophilic infiltration, mucus hyperproduction, and airway hyperresponsiveness but not allergen-specific IgE production. ILC2s contribute to the initiation as well as to the maintenance of the adaptive type 2 immune response. Here, we review the recent progress on our understanding of the role of ILC2s in the immunopathology of allergic asthma, in particular by studies using murine models which have elucidated fundamental mechanisms by which ILC2s act.

Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18(5):716–725. doi:10.1038/nm.2678 CrossRefPubMed

Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma P (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59(5):469–478. doi:10.1111/j.1398-9995.2004.00526.x CrossRefPubMed

Lloyd CM, Hessel EM (2010) Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol 10(12):838–848. doi:10.1038/nri2870 CrossRefPubMed

Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8(3):205–217. doi:10.1038/nri2273 CrossRefPubMed

Takatsu K, Nakajima H (2008) IL-5 and eosinophilia. Curr Opin Immunol 20(3):288–294. doi:10.1016/j.coi.2008.04.001 CrossRefPubMed

Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202:175–190CrossRefPubMed

Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15(6):985–995CrossRefPubMed

Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, Menon S, Seymour B, Jackson C, Kung TT, Brieland JK, Zurawski SM, Chapman RW, Zurawski G, Coffman RL (2002) New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 169(1):443–453CrossRefPubMed

Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F, Vivier E (2013) Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol 13(2):145–149. doi:10.1038/nri3365 CrossRefPubMed

10.

Klein Wolterink RG, Kleinjan A, van Nimwegen M, Bergen I, de Bruijn M, Levani Y, Hendriks RW (2012) Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma. Eur J Immunol 42(5):1106–1116. doi:10.1002/eji.201142018 CrossRefPubMed

11.

Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, Angelosanto JM, Laidlaw BJ, Yang CY, Sathaliyawala T, Kubota M, Turner D, Diamond JM, Goldrath AW, Farber DL, Collman RG, Wherry EJ, Artis D (2011) Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 12(11):1045–1054. doi:10.1031/ni.2131 CrossRefPubMedPubMedCentral

12.

Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM (2010) Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci U S A 107(25):11489–11494. doi:10.1073/pnas.1003988107 CrossRefPubMedPubMedCentral

13.

Oliphant CJ, Hwang YY, Walker JA, Salimi M, Wong SH, Brewer JM, Englezakis A, Barlow JL, Hams E, Scanlon ST, Ogg GS, Fallon PG, McKenzie AN (2014) MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity 41(2):283–295. doi:10.1016/j.immuni.2014.06.016 CrossRefPubMedPubMedCentral

14.

Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, Lahl K, Sparwasser T, Helmby H, Stockinger B (2011) An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 12(11):1071–1077. doi:10.1038/ni.2133 CrossRefPubMedPubMedCentral

15.

Halim TY, Takei F (2014) Isolation and characterization of mouse innate lymphoid cells. Curr Protoc Immunol 106, 3.25.21-23.25.13. doi:10.1002/0471142735.im0325s106, edited by John EColigan [et al.]

16.

Doherty TA, Khorram N, Lund S, Mehta AK, Croft M, Broide DH (2013) Lung type 2 innate lymphoid cells express cysteinyl leukotriene receptor 1, which regulates TH2 cytokine production. J Allergy Clin Immunol 132(1):205–213. doi:10.1016/j.jaci.2013.03.048 CrossRefPubMedPubMedCentral

17.

Doherty TA, Khorram N, Chang JE, Kim HK, Rosenthal P, Croft M, Broide DH (2012) STAT6 regulates natural helper cell proliferation during lung inflammation initiated by Alternaria. Am J Physiol Lung Cell Mol Physiol 303(7):L577–L588. doi:10.1152/ajplung.00174.2012 CrossRefPubMedPubMedCentral

18.

Kim HY, Chang YJ, Subramanian S, Lee HH, Albacker LA, Matangkasombut P, Savage PB, McKenzie AN, Smith DE, Rottman JB, DeKruyff RH, Umetsu DT (2012) Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. J Allergy Clin Immunol 129(1):216–227. doi:10.1016/j.jaci.2011.10.036, e211-216CrossRefPubMed

19.

Van Dyken SJ, Mohapatra A, Nussbaum JC, Molofsky AB, Thornton EE, Ziegler SF, McKenzie AN, Krummel MF, Liang HE, Locksley RM (2014) Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and gammadelta T cells. Immunity 40(3):414–424. doi:10.1016/j.immuni.2014.02.003 CrossRefPubMedPubMedCentral

20.

Mohapatra A, Van Dyken SJ, Schneider C, Nussbaum JC, Liang HE, Locksley RM (2015) Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis. Mucosal Immunol. doi:10.1038/mi.2015.59 PubMedPubMedCentral

21.

Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE, Dekruyff RH, Umetsu DT (2011) Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol 12(7):631–638. doi:10.1038/ni.2045 CrossRefPubMedPubMedCentral

22.

Gorski SA, Hahn YS, Braciale TJ (2013) Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection. PLoS Pathog 9(9), e1003615. doi:10.1371/journal.ppat.1003615 CrossRefPubMedPubMedCentral

23.

Turner JE, Morrison PJ, Wilhelm C, Wilson M, Ahlfors H, Renauld JC, Panzer U, Helmby H, Stockinger B (2013) IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J Exp Med 210(13):2951–2965. doi:10.1084/jem.20130071 CrossRefPubMedPubMedCentral

24.

Licona-Limon P, Kim LK, Palm NW, Flavell RA (2013) TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 14(6):536–542. doi:10.1038/ni.2617 CrossRefPubMed

25.

Halim TY, Krauss RH, Sun AC, Takei F (2012) Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity 36(3):451–463. doi:10.1016/j.immuni.2011.12.020 CrossRefPubMed

26.

Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, Thornton EE, Krummel MF, Chawla A, Liang HE, Locksley RM (2013) Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502(7470):245–248. doi:10.1038/nature12526 CrossRefPubMedPubMedCentral

27.

Barlow JL, McKenzie AN (2014) Type-2 innate lymphoid cells in human allergic disease. Curr Opin Allergy Clin Immunol 14(5):397–403. doi:10.1097/ACI.0000000000000090 CrossRefPubMedPubMedCentral

28.

Xue L, Salimi M, Panse I, Mjosberg JM, McKenzie AN, Spits H, Klenerman P, Ogg G (2014) Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol 133(4):1184–1194. doi:10.1016/j.jaci.2013.10.056 CrossRefPubMedPubMedCentral

29.

Chang JE, Doherty TA, Baum R, Broide D (2014) Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. J Allergy Clin Immunol 133(3):899–901. doi:10.1016/j.jaci.2013.09.020, e893CrossRefPubMed

30.

Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, Levy BD (2013) Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci Transl Med 5(174), 174ra126. doi:10.1126/scitranslmed.3004812 CrossRef

31.

Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464(7293):1367–1370. doi:10.1038/nature08900 CrossRefPubMedPubMedCentral

32.

Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463(7280):540–544. doi:10.1038/nature08636 CrossRefPubMed

33.

Klein Wolterink RG, Serafini N, van Nimwegen M, Vosshenrich CA, de Bruijn MJ, Fonseca Pereira D, Veiga Fernandes H, Hendriks RW, Di Santo JP (2013) Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells. Proc Natl Acad Sci U S A 110(25):10240–10245. doi:10.1073/pnas.1217158110 CrossRefPubMedPubMedCentral

34.

Hardman CS, Panova V, McKenzie AN (2013) IL-33 citrine reporter mice reveal the temporal and spatial expression of IL-33 during allergic lung inflammation. Eur J Immunol 43(2):488–498. doi:10.1002/eji.201242863 CrossRefPubMed

35.

McSorley HJ, Blair NF, Smith KA, McKenzie AN, Maizels RM (2014) Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunol 7(5):1068–1078. doi:10.1038/mi.2013.123 CrossRefPubMedPubMedCentral

36.

Kim BS, Siracusa MC, Saenz SA, Noti M, Monticelli LA, Sonnenberg GF, Hepworth MR, Van Voorhees AS, Comeau MR, Artis D (2013) TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci Transl Med 5(170), 170ra116. doi:10.1126/scitranslmed.3005374 CrossRef

37.

Barlow JL, Peel S, Fox J, Panova V, Hardman CS, Camelo A, Bucks C, Wu X, Kane CM, Neill DR, Flynn RJ, Sayers I, Hall IP, McKenzie AN (2013) IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J Allergy Clin Immunol 132(4):933–941. doi:10.1016/j.jaci.2013.05.012 CrossRefPubMed

38.

Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H (2011) Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 12(11):1055–1062. doi:10.1038/ni.2104 CrossRefPubMed

39.

Mjosberg J, Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, te Velde AA, Fokkens WJ, van Drunen CM, Spits H (2012) The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37(4):649–659. doi:10.1016/j.immuni.2012.08.015 CrossRefPubMed

40.

Salimi M, Barlow JL, Saunders SP, Xue L, Gutowska-Owsiak D, Wang X, Huang LC, Johnson D, Scanlon ST, McKenzie AN, Fallon PG, Ogg GS (2013) A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med 210(13):2939–2950. doi:10.1084/jem.20130351 CrossRefPubMedPubMedCentral

41.

Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U, Williamson PR, Urban JF Jr, Paul WE (2015) IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol 16(2):161–169. doi:10.1038/ni.3078 CrossRefPubMed

42.

Roediger B, Kyle R, Yip KH, Sumaria N, Guy TV, Kim BS, Mitchell AJ, Tay SS, Jain R, Forbes-Blom E, Chen X, Tong PL, Bolton HA, Artis D, Paul WE, Fazekas de St Groth B, Grimbaldeston MA, Le Gros G, Weninger W (2013) Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells. Nat Immunol 14(6):564–573. doi:10.1038/ni.2584 CrossRefPubMedPubMedCentral

43.

Roediger B, Kyle R, Tay SS, Mitchell AJ, Bolton HA, Guy TV, Tan SY, Forbes-Blom E, Tong PL, Koller Y, Shklovskaya E, Iwashima M, McCoy KD, Le Gros G, Fazekas de St Groth B, Weninger W (2015) IL-2 is a critical regulator of group 2 innate lymphoid cell function during pulmonary inflammation. J Allergy Clin Immunol. doi:10.1016/j.jaci.2015.03.043 PubMed

44.

Yu X, Pappu R, Ramirez-Carrozzi V, Ota N, Caplazi P, Zhang J, Yan D, Xu M, Lee WP, Grogan JL (2014) TNF superfamily member TL1A elicits type 2 innate lymphoid cells at mucosal barriers. Mucosal Immunol 7(3):730–740. doi:10.1038/mi.2013.92 CrossRefPubMed

45.

Meylan F, Hawley ET, Barron L, Barlow JL, Penumetcha P, Pelletier M, Sciume G, Richard AC, Hayes ET, Gomez-Rodriguez J, Chen X, Paul WE, Wynn TA, McKenzie AN, Siegel RM (2014) The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells. Mucosal Immunol 7(4):958–968. doi:10.1038/mi.2013.114 PubMed

46.

Meylan F, Richard AC, Siegel RM (2011) TL1A and DR3, a TNF family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation. Immunol Rev 244(1):188–196. doi:10.1111/j.1600-065X.2011.01068.x CrossRefPubMed

47.

Boyce JA (2008) Eicosanoids in asthma, allergic inflammation, and host defense. Curr Mol Med 8(5):335–349CrossRefPubMed

48.

Henderson WR Jr, Lewis DB, Albert RK, Zhang Y, Lamm WJ, Chiang GK, Jones F, Eriksen P, Tien YT, Jonas M, Chi EY (1996) The importance of leukotrienes in airway inflammation in a mouse model of asthma. J Exp Med 184(4):1483–1494CrossRefPubMed

49.

Wenzel SE, Larsen GL, Johnston K, Voelkel NF, Westcott JY (1990) Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis 142(1):112–119. doi:10.1164/ajrccm/142.1.112 CrossRefPubMed

50.

Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K (2001) Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193(2):255–261CrossRefPubMedPubMedCentral

51.

Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN (2002) Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med 8(9):1018–1023. doi:10.1038/nm748 CrossRefPubMed

52.

Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, Barlow JL, Neill DR, Panova V, Koch U, Radtke F, Hardman CS, Hwang YY, Fallon PG, McKenzie AN (2012) Transcription factor RORalpha is critical for nuocyte development. Nat Immunol 13(3):229–236. doi:10.1038/ni.2208 CrossRefPubMedPubMedCentral

53.

O'Byrne PM, Inman MD, Parameswaran K (2001) The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol 108(4):503–508CrossRefPubMed

54.

Halim TY, MacLaren A, Romanish MT, Gold MJ, McNagny KM, Takei F (2012) Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. Immunity 37(3):463–474. doi:10.1016/j.immuni.2012.06.012 CrossRefPubMed

55.

Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210(3):535–549. doi:10.1084/jem.20121964 CrossRefPubMedPubMedCentral

56.

Barlow JL, Bellosi A, Hardman CS, Drynan LF, Wong SH, Cruickshank JP, McKenzie AN (2012) Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J Allergy Clin Immunol 129(1):191–198. doi:10.1016/j.jaci.2011.09.041, e191-194CrossRefPubMed

57.

Blanchard C, Rothenberg ME (2009) Biology of the eosinophil. Adv Immunol 101:81–121. doi:10.1016/S0065-2776(08)01003-1 CrossRefPubMedPubMedCentral

58.

Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35. doi:10.1038/nri978 CrossRefPubMed

59.

Byers DE, Holtzman MJ (2011) Alternatively activated macrophages and airway disease. Chest 140(3):768–774. doi:10.1378/chest.10-2132 CrossRefPubMedPubMedCentral

60.

Roy A, Ganesh G, Sippola H, Bolin S, Sawesi O, Dagalv A, Schlenner SM, Feyerabend T, Rodewald HR, Kjellen L, Hellman L, Abrink M (2014) Mast cell chymase degrades the alarmins heat shock protein 70, biglycan, HMGB1, and interleukin-33 (IL-33) and limits danger-induced inflammation. J Biol Chem 289(1):237–250. doi:10.1074/jbc.M112.435156 CrossRefPubMed

61.

Kim BS, Wang K, Siracusa MC, Saenz SA, Brestoff JR, Monticelli LA, Noti M, Tait Wojno ED, Fung TC, Kubo M, Artis D (2014) Basophils promote innate lymphoid cell responses in inflamed skin. J Immunol 193(7):3717–3725. doi:10.4049/jimmunol.1401307 CrossRefPubMedPubMedCentral

62.

Kamijo S, Takeda H, Tokura T, Suzuki M, Inui K, Hara M, Matsuda H, Matsuda A, Oboki K, Ohno T, Saito H, Nakae S, Sudo K, Suto H, Ichikawa S, Ogawa H, Okumura K, Takai T (2013) IL-33-mediated innate response and adaptive immune cells contribute to maximum responses of protease allergen-induced allergic airway inflammation. J Immunol 190(9):4489–4499. doi:10.4049/jimmunol.1201212 PubMed

63.

Gold MJ, Antignano F, Halim TY, Hirota JA, Blanchet MR, Zaph C, Takei F, McNagny KM (2014) Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2-inducing allergen exposures. J Allergy Clin Immunol 133(4):1142–1148. doi:10.1016/j.jaci.2014.02.033 CrossRefPubMed

64.

Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I, McNagny KM, McKenzie AN, Takei F (2014) Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40(3):425–435. doi:10.1016/j.immuni.2014.01.011 CrossRefPubMedPubMedCentral

65.

Paul WE, Zhu J (2010) How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol 10(4):225–235. doi:10.1038/nri2735 CrossRefPubMedPubMedCentral

66.

KleinJan A, Klein Wolterink RG, Levani Y, de Bruijn MJ, Hoogsteden HC, van Nimwegen M, Hendriks RW (2014) Enforced expression of Gata3 in T cells and group 2 innate lymphoid cells increases susceptibility to allergic airway inflammation in mice. J Immunol 192(4):1385–1394. doi:10.4049/jimmunol.1301888 CrossRefPubMed

67.

van Panhuys N, Tang SC, Prout M, Camberis M, Scarlett D, Roberts J, Hu-Li J, Paul WE, Le Gros G (2008) In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation. Proc Natl Acad Sci U S A 105(34):12423–12428. doi:10.1073/pnas.0806372105 CrossRefPubMedPubMedCentral

68.

Mirchandani AS, Besnard AG, Yip E, Scott C, Bain CC, Cerovic V, Salmond RJ, Liew FY (2014) Type 2 innate lymphoid cells drive CD4+ Th2 cell responses. J Immunol 192(5):2442–2448. doi:10.4049/jimmunol.1300974 CrossRefPubMed

69.

Drake LY, Iijima K, Kita H (2014) Group 2 innate lymphoid cells and CD4 T cells cooperate to mediate type 2 immune response in mice. Allergy. doi:10.1111/all.12446 PubMedPubMedCentral

70.

Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FX, Yao Z, Cao W, Liu YJ (2005) TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 202(9):1213–1223CrossRefPubMedPubMedCentral

71.

Krishnamoorthy N, Burkett PR, Dalli J, Abdulnour RE, Colas R, Ramon S, Phipps RP, Petasis NA, Kuchroo VK, Serhan CN, Levy BD (2015) Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J Immunol 194(3):863–867. doi:10.4049/jimmunol.1402534 CrossRefPubMed

72.

Christianson CA, Goplen NP, Zafar I, Irvin C, Good JT Jr, Rollins DR, Gorentla B, Liu W, Gorska MM, Chu H, Martin RJ, Alam R (2015) Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33. J Allergy Clin Immunol 136(1):59–68. doi:10.1016/j.jaci.2014.11.037, e14CrossRefPubMedPubMedCentral

73.

Fukuoka A, Futatsugi-Yumikura S, Takahashi S, Kazama H, Iyoda T, Yoshimoto T, Inaba K, Nakanishi K, Yonehara S (2013) Identification of a novel type 2 innate immunocyte with the ability to enhance IgE production. Int Immunol 25(6):373–382. doi:10.1093/intimm/dxs160 CrossRefPubMed

74.

Maazi H, Patel N, Sankaranarayanan I, Suzuki Y, Rigas D, Soroosh P, Freeman GJ, Sharpe AH, Akbari O (2015) ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity. Immunity 42(3):538–551. doi:10.1016/j.immuni.2015.02.007 CrossRefPubMedPubMedCentral

75.

Allakhverdi Z, Comeau MR, Smith DE, Toy D, Endam LM, Desrosiers M, Liu YJ, Howie KJ, Denburg JA, Gauvreau GM, Delespesse G (2009) CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation. J Allergy Clin Immunol 123(2):472–478. doi:10.1016/j.jaci.2008.10.022 CrossRefPubMed

76.

Ying S, O'Connor B, Ratoff J, Meng Q, Mallett K, Cousins D, Robinson D, Zhang G, Zhao J, Lee TH, Corrigan C (2005) Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol 174(12):8183–8190CrossRefPubMed

77.

Prefontaine D, Nadigel J, Chouiali F, Audusseau S, Semlali A, Chakir J, Martin JG, Hamid Q (2010) Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol 125(3):752–754. doi:10.1016/j.jaci.2009.12.935 CrossRefPubMed

78.

Corrigan CJ, Wang W, Meng Q, Fang C, Eid G, Caballero MR, Lv Z, An Y, Wang YH, Liu YJ, Kay AB, Lee TH, Ying S (2011) Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses. J Allergy Clin Immunol 128(1):116–124. doi:10.1016/j.jaci.2011.03.043 CrossRefPubMed

79.

Ober C, Yao TC (2011) The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 242(1):10–30. doi:10.1111/j.1600-065X.2011.01029.x CrossRefPubMedPubMedCentral

80.

Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, Eng C, Stern DA, Celedon JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van Den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque MU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Li X, Calhoun WJ, Castro M, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske RF Jr, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Mexico City Childhood Asthma S, Gilliland FD, Children's Health S, Study H, Burchard EG, Genetics of Asthma in Latino Americans Study SoG-E, Admixture in Latino A, Study of African Americans AG, Environments, Martinez FD, Childhood Asthma R, Education N, Weiss ST, Childhood Asthma Management P, Williams LK, Study of Asthma P, Pharmacogenomic Interactions by R-E, Barnes KC, Genetic Research on Asthma in African Diaspora S, Ober C, Nicolae DL (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43(9):887–892. doi:10.1038/ng.888 CrossRefPubMedPubMedCentral

81.

Jung JS, Park BL, Cheong HS, Bae JS, Kim JH, Chang HS, Rhim T, Park JS, Jang AS, Lee YM, Kim KU, Uh ST, Na JO, Kim YH, Park CS, Shin HD (2009) Association of IL-17RB gene polymorphism with asthma. Chest 135(5):1173–1180. doi:10.1378/chest.08-1595 CrossRefPubMed

82.

Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO, Consortium G (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363(13):1211–1221. doi:10.1056/NEJMoa0906312 CrossRefPubMedPubMedCentral

83.

Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, Nair P, Sehmi R (2016) Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol 137(1):75–86. doi:10.1016/j.jaci.2015.05.037, e78CrossRefPubMed

84.

Nagakumar P, Denney L, Fleming L, Bush A, Lloyd CM, Saglani S (2015) Type 2 innate lymphoid cells in induced sputum from children with severe asthma. J Allergy Clin Immunol. doi:10.1016/j.jaci.2015.06.038 PubMed

85.

Bartemes KR, Kephart GM, Fox SJ, Kita H (2014) Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol 134(3):671–678. doi:10.1016/j.jaci.2014.06.024, e674CrossRefPubMedPubMedCentral

86.

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, de Wang Y, Wormald PJ (2012) EPOS 2012: European position paper on rhinosinusitis and nasal polyps, a summary for otorhinolaryngologists. Rhinology 50(1):1–12. doi:10.4193/Rhino50E2 PubMed

87.

Miljkovic D, Bassiouni A, Cooksley C, Ou J, Hauben E, Wormald PJ, Vreugde S (2014) Association between group 2 innate lymphoid cells enrichment, nasal polyps and allergy in chronic rhinosinusitis. Allergy 69(9):1154–1161. doi:10.1111/all.12440 CrossRefPubMed

88.

Shaw JL, Fakhri S, Citardi MJ, Porter PC, Corry DB, Kheradmand F, Liu YJ, Luong A (2013) IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps. Am J Respir Crit Care Med 188(4):432–439. doi:10.1164/rccm.201212-2227OC CrossRefPubMed

89.

Van Bruaene N, Perez-Novo CA, Basinski TM, Van Zele T, Holtappels G, De Ruyck N, Schmidt-Weber C, Akdis C, Van Cauwenberge P, Bachert C, Gevaert P (2008) T-cell regulation in chronic paranasal sinus disease. J Allergy Clin Immunol 121(6):1435–1441. doi:10.1016/j.jaci.2008.02.018, 1441.e1431-1433CrossRefPubMed

90.

Nagarkar DR, Poposki JA, Tan BK, Comeau MR, Peters AT, Hulse KE, Suh LA, Norton J, Harris KE, Grammer LC, Chandra RK, Conley DB, Kern RC, Schleimer RP, Kato A (2013) Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. J Allergy Clin Immunol 132(3):593–600. doi:10.1016/j.jaci.2013.04.005, e512CrossRefPubMedPubMedCentral

91.

Peng W, Novak N (2014) Recent developments in atopic dermatitis. Curr Opin Allergy Clin Immunol 14(5):417–422. doi:10.1097/ACI.0000000000000094 CrossRefPubMed

92.

Savinko T, Matikainen S, Saarialho-Kere U, Lehto M, Wang G, Lehtimaki S, Karisola P, Reunala T, Wolff H, Lauerma A, Alenius H (2012) IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Investig Dermatol 132(5):1392–1400. doi:10.1038/jid.2011.446 CrossRefPubMed

93.

Brandt EB, Sivaprasad U (2011) Th2 cytokines and atopic dermatitis. J Clin Cell Immunol 2(3):110CrossRefPubMedPubMedCentral

94.

Wu CA, Peluso JJ, Zhu L, Lingenheld EG, Walker ST, Puddington L (2010) Bronchial epithelial cells produce IL-5: implications for local immune responses in the airways. Cell Immunol 264(1):32–41. doi:10.1016/j.cellimm.2010.04.008 CrossRefPubMedPubMedCentral

95.

Enomoto Y, Orihara K, Takamasu T, Matsuda A, Gon Y, Saito H, Ra C, Okayama Y (2009) Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. J Allergy Clin Immunol 124(5):913–920. doi:10.1016/j.jaci.2009.08.044, e911-917CrossRefPubMed

Title: Type 2 innate lymphoid cells: at the cross-roads in allergic asthma
Publication date: 01-07-2016
Published in: Seminars in Immunopathology / Issue 4/2016
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-016-0556-2

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