Research Article: IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

Date Published: April 7, 2016

Publisher: Public Library of Science

Author(s): José L. Reyes, Maria R. Fernando, Fernando Lopes, Gabriella Leung, Nicole L. Mancini, Chelsea E. Matisz, Arthur Wang, Derek M. McKay, Debroski R. Herbert.

http://doi.org/10.1371/journal.ppat.1005481

Abstract

Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

Partial Text

Interleukin (IL)-22, a member of the IL-10 family, is produced predominantly by innate (NK cells (NK22), γδ T cells, innate lymphoid cells type 3 (ILC3s) and adaptive (CD4+ Th22 and Th17, CD8+ T cells) immune cells: a non-immune source of IL-22 has not been described. The heterodimeric IL-22 receptor consists of the IL-10R2 subunit and the unique IL-22R1 subunit, and is restricted to non-hematopoetic cells (e.g. hepatocytes and epithelium of the gastrointestinal tract) [1]. Thus, IL-22 is an immune cell-derived mediator that acts exclusively on non-immune cells and as such is an attractive target for therapeutic intervention [2, 3].

 

Source:

http://doi.org/10.1371/journal.ppat.1005481

 

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