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

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. © 2016 reyes et al.