IL‐33 citrine reporter mice reveal the temporal and spatial expression of IL‐33 during allergic lung inflammation

Abstract

Interleukin‐33 (IL‐33) is an IL‐1 family cytokine that signals via its receptor T1/ST2, and is a key regulator of inflammation, notably the type‐2 response implicated in allergic asthma. Critical to our understanding of the role of IL‐33 is the identification of the cellular sources of IL‐33. Although progress has been made in this area, the development of a robust live cell reporter of expression would allow the localisation of IL‐33 during ongoing immune responses. We have generated a fluorescent reporter mouse line, Il33 Cit/+ , to define the expression profile of IL‐33 in vivo and demonstrate its temporal and spatial expression during experimental allergic asthma responses. We found that type‐2 pneumocytes constitute the major source of IL‐33 upon allergic lung inflammation following exposure to OVA, fungal extract or ragweed pollen. Using Il33 Cit/Cit mice (IL‐33‐deficient), we establish a role for IL‐33 early in the initiation of type‐2 responses and the induction of nuocytes (ILC2). We also demonstrate a potential mechanism of action by which IL‐33 rapidly initiates type‐2 immune responses. Il33 Cit/+ mice have enabled new insights into the initiation of type‐2 responses and will provide an important tool for further dissection of this important inflammatory pathway in vivo.

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References 36

1. 1.

   Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 1989;7:145-173.

   Not in our library10.1146/annurev.iy.07.040189.001045

2. 2.

   McLane MP, Haczku A, van de Rijn M, Weiss C, Ferrante V, MacDonald D, Renauld JC, et al. Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice. Am. J. Respir. Cell Mol. Biol. 1998;19:713-720.

   Not in our library10.1165/ajrcmb.19.5.3457

3. 3.

   Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258-2261.

   Not in our library10.1126/science.282.5397.2258

4. 4.

   Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat. Rev. Immunol. 2010;10:225-235.

   Not in our library10.1038/nri2735

5. 5.

   Voehringer D, Shinkai K, Locksley RM. Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity. 2004;20:267-277.

   Not in our library10.1016/s1074-7613(04)00026-3

6. 6.

   Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat. Immunol. 2010;11:577-584.

   Not in our library10.1038/ni.1892

7. 7.

   Prefontaine D, Lajoie-Kadoch S, Foley S, Audusseau S, Olivenstein R, Halayko AJ, Lemiere C, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J. Immunol. 2009;183:5094-5103.

   Not in our library10.4049/jimmunol.0802387

8. 8.

   Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J. Exp. Med. 2007;204:1837-1847.

   Not in our library10.1084/jem.20070406

9. 9.

   Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15:985-995.

   Not in our library10.1016/s1074-7613(01)00243-6

10. 10.

    Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, 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;23:479-490.

    Not in our library10.1016/j.immuni.2005.09.015

11. 11.

    Luthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, Brumatti G, et al. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity. 2009;31:84-98.

    Not in our library10.1016/j.immuni.2009.05.007

12. 12.

    Talabot-Ayer D, Lamacchia C, Gabay C, Palmer G. Interleukin-33 is biologically active independently of caspase-1 cleavage. J. Biol. Chem. 2009;284:19420-19426.

    Not in our library10.1074/jbc.m901744200

13. 13.

    Cayrol C, Girard JP. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc. Natl. Acad. Sci. USA. 2009;106:9021-9026.

    Not in our library10.1073/pnas.0812690106

14. 14.

    Barlow JL, Bellosi A, Hardman CS, Drynan LF, Wong SH, Cruickshank JP, McKenzie AN. Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J. Allergy Clin. Immunol. 129;191-198.

    Not in our library10.1016/j.jaci.2011.09.041

15. 15.

    Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010;464:1367-1370.

    Not in our library10.1038/nature08900

16. 16.

    Kim HY, Chang YJ, Subramanian S, Lee HH, Albacker LA, Matangkasombut P, Savage PB, et al. Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. J. Allergy Clin. Immunol. 2012;129:216-227.

    Not in our library10.1016/j.jaci.2011.10.036

17. 17.

    Moro K, Koyasu S. Identification of natural helper cell. Arerugi. 2010;59:810-814.

    Not in our library

18. 18.

    Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc. Natl. Acad. Sci. USA. 2010;107:11489-11494.

    Not in our library10.1073/pnas.1003988107

19. 19.

    Min B, Prout M, Hu-Li J, Zhu J, Jankovic D, Morgan ES, Urban JF, et al. Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite. J. Exp. Med. 2004;200:507-517.

    Not in our library10.1084/jem.20040590

20. 20.

    Roussel L, Erard M, Cayrol C, Girard JP. Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket. EMBO Rep. 2008;9:1006-1012.

    Not in our library10.1038/embor.2008.145

21. 21.

    Fahy JV, Locksley RM. The airway epithelium as a regulator of Th2 responses in asthma. Am. J. Respir. Crit. Care Med. 2011;184:390-392.

    Not in our library10.1164/rccm.201107-1258ed

22. 22.
    The IL-1-Like Cytokine IL-33 Is Constitutively Expressed in the Nucleus of Endothelial Cells and Epithelial Cells In Vivo: A Novel ‘Alarmin’? · 2008

    No notice
23. 23.

    Polumuri SK, Jayakar GG, Shirey KA, Roberts ZJ, Perkins DJ, Pitha PM, Vogel SN. Transcriptional regulation of murine IL-33 by TLR and non-TLR agonists. J. Immunol. 2012;189:50-60.

    Not in our library10.4049/jimmunol.1003554

24. 24.

    Wills-Karp M, Rani R, Dienger K, Lewkowich I, Fox JG, Perkins C, Lewis L, et al. Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. J. Exp. Med. 2012;209:607-622.

    Not in our library10.1084/jem.20110079

25. 25.

    Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, Barlow JL, et al. Transcription factor RORalpha is critical for nuocyte development. Nat. Immunol. 2012;13:229-236.

    Not in our library10.1038/ni.2208

26. 26.

    Pichery M, Mirey E, Mercier P, Lefrancais E, Dujardin A, Ortega N, Girard JP. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J. Immunol. 2012;188:3488-3495.

    Not in our library10.4049/jimmunol.1101977

27. 27.

    Lloyd CM. IL-33 family members and asthma—bridging innate and adaptive immune responses. Curr. Opin. Immunol. 2010;22:800-806.

    Not in our library10.1016/j.coi.2010.10.006

28. 28.

    Prefontaine D, Nadigel J, Chouiali F, Audusseau S, Semlali A, Chakir J, Martin JG, et al. Increased IL-33 expression by epithelial cells in bronchial asthma. J. Allergy Clin. Immunol. 2010;125:752-754.

    Not in our library10.1016/j.jaci.2009.12.935

29. 29.

    Orr G, Panther DJ, Cassens KJ, Phillips JL, Tarasevich BJ, Pounds JG. Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane. Toxicol. Appl. Pharmacol. 2009;236:210-220.

    Not in our library10.1016/j.taap.2009.01.022

30. 30.

    Demaio L, Tseng W, Balverde Z, Alvarez JR, Kim KJ, Kelley DG, Senior RM, et al. Characterization of mouse alveolar epithelial cell monolayers. Am. J. Physiol. Lung Cell Mol. Physiol. 2009;296:L1051-1058.

    Not in our library10.1152/ajplung.00021.2009

31. 31.

    Kouzaki H, Iijima K, Kobayashi T, O'Grady SM, Kita H. The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J. Immunol. 2011;186:4375-4387.

    Not in our library10.4049/jimmunol.1003020

32. 32.

    Dobbs LG, Johnson MD. Alveolar epithelial transport in the adult lung. Respir. Physiol. Neurobiol. 2007;159:283-300.

    Not in our library10.1016/j.resp.2007.06.011

33. 33.

    Baekvad-Hansen M, Nordestgaard BG, Tybjaerg-Hansen A, Dahl M. Two novel mutations in surfactant protein-C, lung function and obstructive lung disease. Respir. Med. 2010;104:418-425.

    Not in our library10.1016/j.rmed.2009.10.012

34. 34.

    Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Taki Y, et al. Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc. Natl. Acad. Sci. USA. 2012;109:3451-3456.

    Not in our library10.1073/pnas.1201042109

35. 35.

    Bartemes KR, Iijima K, Kobayashi T, Kephart GM, McKenzie AN, Kita H. IL-33-responsive lineage- CD25 +CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs. J. Immunol. 2012;188:1503-1513.

    Not in our library10.4049/jimmunol.1102832

36. 36.

    Barlow JL, Flynn RJ, Ballantyne SJ, McKenzie AN. Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyperreactivity. Clin. Exp. Allergy. 2011;41:1447-1455.

    Not in our library10.1111/j.1365-2222.2011.03806.x

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