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Review
. 2021 Nov 1;49(5):2371-2380.
doi: 10.1042/BST20210535.

Type 2 immunity in intestinal homeostasis and inflammatory bowel disease

Xinxin Luo  1   2 , Eduardo J Villablanca  1   2
Affiliations
Review

Type 2 immunity in intestinal homeostasis and inflammatory bowel disease

Xinxin Luo et al. Biochem Soc Trans. .

Abstract

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (TH2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

Keywords: ILC2; TH2; inflammatory bowel disease; mucosal immunology; type 2 immunity.

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Conflict of interest statement

E.J.V. has received research grants from F. Hoffmann-La Roche.

Figures

Figure 1.
Figure 1.. Type 2 immune responses in the intestinal mucosa from healthy and inflammatory bowel disease (IBD).
Type 2 immune responses mediated by TH2 and ILC2 during homoeostatic conditions, inflammation and tissue repair: (a) At steady-state conditions, type 2 cytokines produced by either ILC2 or TH2 orchestrate epithelial homeostasis. Type 2 immune responses can promote crypt stemness and the epithelial cell differentiation towards the tuft and/or goblet cell lineage. This process is crucial to maintain a healthy mucus layer and eventually the integrity of the intestinal barrier. Epithelial cells derived alarmins (IL-25, CysLTs, IL-33, and TSLP) activate ILC2 promoting the establishment of tolerogenic immune responses. (b) In the inflamed intestine during IBD, ILC2, and TH2 accumulate in inflamed lesions. Damaged epithelium permeability and loss of the mucus layer might result in commensals bacterial translocation and dissemination. Dissemination of bacteria result in NOD2-dependent activation which results in the production of IL-33. Eventually, ILC2s are activated by IL-33 and in turn produce IL-5 and IL-13, which fuel chronic ileitis. (c) During the process of tissue repair, IL-4 or IL-13 combined with apoptotic cells stimulate macrophages to promote wound healing and tissue remodeling.
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References

    1. Ananthakrishnan, A.N., Bernstein, C.N., Iliopoulos, D., Macpherson, A., Neurath, M.F., Ali, R.A.R.et al. (2018) Environmental triggers in IBD: a review of progress and evidence. Nat. Rev. Gastroenterol. Hepatol. 15, 39–49 10.1038/nrgastro.2017.136 - DOI - PubMed
    1. Imam, T., Park, S., Kaplan, M.H. and Olson, M.R. (2018) Effector T helper cell subsets in inflammatory bowel diseases. Front. Immunol. 9, 1212 10.3389/fimmu.2018.01212 - DOI - PMC - PubMed
    1. Mohammadi, R., Hosseini-Safa, A., Ehsani Ardakani, M.J. and Rostami-Nejad, M. (2015) The relationship between intestinal parasites and some immune-mediated intestinal conditions. Gastroenterol. Hepatol. Bed. Bench. 8, 123–131 PMID: - PMC - PubMed
    1. Salgame, P., Yap, G.S. and Gause, W.C. (2013) Effect of helminth-induced immunity on infections with microbial pathogens. Nat. Immunol. 14, 1118–1126 10.1038/ni.2736 - DOI - PMC - PubMed
    1. Anthony, R.M., Rutitzky, L.I., Urban, J.F., Stadecker, M.J. and Gause, W.C. (2007) Protective immune mechanisms in helminth infection. Nat. Rev. Immunol. 7, 975–987 10.1038/nri2199 - DOI - PMC - PubMed

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