Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells.
FEBS Open Bio
; 11(5): 1406-1416, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33728805
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Hepatitis Autoinmune
/
Receptor 2 Celular del Virus de la Hepatitis A
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
FEBS Open Bio
Año:
2021
Tipo del documento:
Article
País de afiliación:
China