IL-10 modulates intestinal damage and epithelial cell apoptosis in T cell-mediated enteropathy

Abstract

In vivo T cell activation by anti-CD3 monoclonal antibody (mAb) results in intestinal damage characterized by loss of villi and epithelial cell apoptosis. The role of the increased interleukin (IL)-10 released during this process is not clear. We assessed the effects of IL-10 on T cell-induced mucosal damage in vivo using IL-10-deficient C57BL/6 [IL-10 knockout (KO)] mice. IL-10 KO and wild-type C57BL/6 mice were injected with anti-CD3 mAb and observed for diarrhea. Changes in serum cytokine levels were measured by ELISA. Histological changes and epithelial cell apoptosis were analyzed on hematoxylin- and eosin-stained tissue sections. Fas expression on intestinal epithelial cells was assessed by flow cytometry analysis of freshly isolated intestinal epithelial cells. Anti-CD3-treated IL-10 KO mice developed more severe diarrhea, a greater loss of intestinal villi, and an increase in the numbers of apoptotic cells in the crypt epithelium. This difference in IL-10 KO mice was associated with an increase in serum tumor necrosis factor-alpha and interferon-gamma levels and with an increase in Fas expression on fresh, isolated, small intestinal epithelial cells. In addition, the enhanced intestinal tissue damage induced by anti-CD3 in IL-10 KO mice was significantly diminished by treatment with recombinant murine IL-10. Therefore, the lack of IL-10 allowed for an increased T cell-induced intestinal tissue damage, and this was associated with an increase in T cell cytokine release and an increase in epithelial cell Fas expression.

Resistance of C57BL/6 Mice to Amoebiasis Is Mediated by Nonhemopoietic Cells but Requires Hemopoietic IL-10 Production

“…The epithelium of IL-10 Ϫ/Ϫ mice exhibits defects in synthesis of Muc2 (23), a major component of human colonic mucus that limits E. histolytica adherence to host cells (32). Finally, the epithelium of IL-10 Ϫ/Ϫ mice can be predisposed toward increased apoptosis (14), and these cellular corpses could serve as fuel for the amoeba as happens in vitro (33,34). Another intriguing possibility is that trophozoites, being the tissue phase of the parasite, benefit from an IL-10-deficient proinflammatory state; for instance, TNF-␣ (though TNF message was not increased in Table I) is known to promote E. histolytica chemotaxis, adherence, and trophozoite-induced epithelial damage (6,35,36).…”

“…We examined the role of IL-10, because IL-10 regulates the host immune response to gut flora (10 -12) and prevents diverse lymphoid and epithelial defects (13,14). Through this work we find that B6 resistance to intestinal E. histolytica infection occurs at the nonhemopoietic level, yet that the protective capacity of this compartment is maintained via hemopoietic IL-10.…”

“…We next examined the outcome of infection in IL-10 Ϫ/Ϫ mice on the resistant C57BL/6 background, because these mice acquire abundant defects in their epithelium (13,14,(21)(22)(23). When sacrificed at 9 -10 days postchallenge, B6 IL-10-deficient mice exhibited a significantly higher amoeba score, inflammation score, and culturepositive rate than their WT counterparts (Fig.…”

Time-resolved Quantitative Proteome Analysis of In Vivo Intestinal Development

“…At 1 D, 7 D, 14 D, and 35 D, one mouse per litter (3 females, 3 males) was sacrificed by cervical dislocation and intestinal epithelial cells were isolated as described previously (22,23), with slight modifications. Briefly, the jejunum was dissected and fat and Peyer's patches were removed.…”

Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage

“…By acting as a TH2 cytokine, however, it generally protects against the action of TH1 cytokines (Zhou et al 2004). There are several pathways that may be responsible for the anti-inflammatory function of IL-10.…”