Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease.
Augmented intestinal T cells, especially CD4(+)T cells, are involved in the pathogenesis of inflammatory bowel disease (IBD). We used a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model to investigate whether Tim-3, a negative regulator of CD4(+)T cells, is involved in the suppression of IBD. We found that blocking the Tim-3 signal pathway exacerbated TNBS-induced colitis, as shown by increased weight loss and aggravated tissue injury. Blockade of the Tim-3 pathway resulted in an increase in Tim-3(+)CD4T cells, a biased T effector cell response, and a decrease in Treg cells. It also resulted in an altered profile of co-stimulatory molecules expressed on lymphocytes, which partially explained the biased polarization of different T cell subsets. Our data suggest that the Tim-3 pathway is highly involved in the negative regulation of IBD. A better understanding of this pathway may shed new light on the pathogenesis of this disease.
Li
Xia
X
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
Chen
Guojiang
G
Li
Yurong
Y
Wang
Renxi
R
Wang
Liyan
L
Lin
Zhou
Z
Gao
Xudong
X
Feng
Jiannan
J
Ma
Yuanfang
Y
Shen
Beifen
B
Li
Yan
Y
Han
Gencheng
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D016207:Cytokines; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; D014302:Trinitrobenzenesulfonic Acid