Effect of Med1 on T cell development and CD4 + T cell differentiation in immune response.

Autor:	Zheng H; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061. huiqiangzheng@163.com.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061. huiqiangzheng@163.com.; Department of Laboratory Medicine, Xi'an Chest Hospital, Xi'an 710100. huiqiangzheng@163.com., Jiao A; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Liu H; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Lei L; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Ding R; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Feng Z; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Zhang D; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061., Zhang L; Suzhou Institute of Systems Medicine, Suzhou Jiangshu 215123., Zhang B; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061. bj.zhang@xjtu.edu.cn.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061. bj.zhang@xjtu.edu.cn.; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China. bj.zhang@xjtu.edu.cn.
Jazyk:	English; Chinese
Zdroj:	Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences [Zhong Nan Da Xue Xue Bao Yi Xue Ban] 2023 Sept 28; Vol. 48 (9), pp. 1296-1303.
DOI:	10.11817/j.issn.1672-7347.2023.220633
Abstrakt:	Objectives: The differentiation of CD4 + T cells is regulated by a complex and fine signaling pathway composed of many molecules during immune response, and the molecular mechanism for regulating T-bet expression is unclear. Mediator complex subunit 1 (Med1) can combine with a variety of co-factors to regulate gene transcription, promote cell proliferation and survival, and affect invariant natural killer T cell (iNKT) development. This study aims to investigate the effect of Med1 on T cell development and CD4 + T cell differentiation in immune response. Methods: Mice with T cell-specific knockout of Med1 gene (Med1 F/F CD4cre + , KO) were constructed and verified. The percentage and number of CD4 + and CD8 + T cells in thymus, spleen, and lymph nodes of KO mice and control (Con) mice (Med1 F/F CD4cre - ) were detected by flow cytometry. After 8 days of infection with lymphocytic choriomeningitis virus (LCMV), the percentage and number of CD4 + T cells or antigen-specific (GP66 + ) CD4 + T cells, the percentage and number of Th1 cells (Ly6c + PSGL1 + ) in CD4 + T cells or antigen-specific CD4 + T cells were examined in the spleen of mice. Moreover, the fluorescence intensity of T-bet in CD4 + T cells or antigen-specific CD4 + T cells was analyzed. Results: Compared with the Con group, the percentage and number of CD4 + T cells and CD8 + T cells in the thymus, CD4 + T cells in the spleen and lymph nodes of the KO group showed no significant differences (all P >0.05), but the percentage and number of CD8 + T cells in the spleen and lymph nodes of the KO group were diminished significantly (all P <0.05). After 8 days of infection with LCMV, there was no significant difference in the percentage and number of CD4 + T cells or antigen-specific CD4 + T cells in the spleen between the KO group and the Con group (all P >0.05), while in comparison with the Con group, the percentage and number of Th1 cells in CD4 + T cells or antigen-specific CD4 + T cells, and the expression of T-bet in CD4 + T cells or antigen-specific CD4 + T cells were significantly reduced in the spleen of the KO group (all P <0.05). Conclusions: Specific knockout of Med1 in T cells does not affect the development of CD4 + and CD8 + T cells in the thymus, but does affect the maintenance of peripheral CD8 + T cells. In the immune response, Med1 gene deletion affects the expression of transcription factor T-bet, which in turn to reduce Th1 cell differentiation.
Databáze:	MEDLINE
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