IL-10 modulates intestinal damage and epithelial cell apoptosis in T cell-mediated enteropathy.
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.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Pengfei
P
Zhou
Cathy
C
Streutker
Rajka
R
Borojevic
Yufa
Y
Wang
Ken
K
Croitoru
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001831:Body Temperature / Q000235:genetics / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D011994:Recombinant Proteins; D019014:fas Receptor; D016753:Interleukin-10