T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell suppression in various autoimmune diseases, such as chronic inflammatory liver disease. However, the regulatory effect of Tim-3 on Th17 cells in autoimmune hepatitis (AIH) is incompletely understood. Here, we studied the expression and function of Tim-3 in T cells in AIH patients and in a Con A (concanavalin A)-induced mouse AIH model. We report that the frequency of CD4+Tim-3+ T cells in peripheral blood samples of AIH patients was lower than that in the control group. The p38/MKP-1 and p-JNK pathways were activated, and the expression of interleukin-17A protein was elevated in patients with AIH. Furthermore, the extent of pathological damage in the livers of mice with a blocked Tim-3 signaling pathway (anti-Tim-3 group) was markedly increased and correlated with elevated alanine aminotransferase and aspartate aminotransferase levels. In addition, the frequency of CD4+ IL-17+ T (Th17) cells in the anti-Tim-3 group was increased, while that in mice with blocked p38 activity was decreased. Finally, the expression of MKP-1 (p-p38) gradually increased in the control, Con A, and anti-Tim-3 groups, but the levels of interleukin-17A were decreased in the p38-blocked group. In summary, our results suggest that Tim-3 suppresses AIH by regulating Th17 cells through the p38/MKP-1 pathway.
CITATION STYLE
Wu, H., Tang, S., Zhou, M., Xue, J., Yu, Z., & Zhu, J. (2021). Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells. FEBS Open Bio, 11(5), 1406–1416. https://doi.org/10.1002/2211-5463.13148
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