组蛋白去乙酰化酶3对恒定型自然杀伤性T细胞发育和功能的调控作用

doi:10.13481/j.1671-587x.20200201

Abstract

Abstract: Objective: To investigate the effects of histone deacetylation enzyme 3 (HDAC3) on the quantity, developmental phenotypes and cytokine production function of the invariant nature killer T cells (iNKT), and to determine the regulatory effects of HDAC3 on the development and function of the iNKT cells. Methods: The T cell-specific hdac3 gene knockout (HDAC3KO) mice and their wild type normal control (WT) mice were used, and 3-5 mice were selected from every kind of mice in experiment. The lymphocytes from the thymus, spleen, lymph nodes and liver of the HDAC3KO and WT mice were separated, and the effects of HDAC3 on the number and developmental phenotypes of the iNKT cells were detected by cell surface antibody staining and flow cytometry methods. The experiment was repeated at least three times. The HDAC3KO mice and their homologous B6.SJL mice were used in the mixed hematopoietic chimerism experiment, and 4-6 mice were selected from every kind of mice. The bone marrow cells from HDAC3KO and B6.SJL mice were extracted, and after mixed together they were injected into the γ-ray irradiated B6.SJL mice via tail vein to prepare the bone marrow mixed chimeric models. Eight weeks later,the production and development of iNKT cells in the thymus from different bone marrows were detected by flow cytometry. The experiment was repeated for three times. The HDAC3KO and WT mice (3-5 mice from every kind of mice) were selected and introperitoneally injected by iNKT cell specific stimulator α-Galcer; 4 h later, the spleen lymphocytes and serum were collected,and the cytokine levels in the iNKT cells after treated with HDAC3 were detected by intracellular staining, flow cytometry and ELISA methods. The experiment was repeated at least 3 times. Results: Compared with the WT mice, the ratios and the number of iNKT cells in the thymus and peripheral immune organs of the HDAC3KO mice were significantly decreased(P<0.05);the ratios of CD44-NK1.1- and CD44+NK1.1-cells in the iNKT cells in thymus of the HDAC3KO mice were significantly increased(P<0.05); and the ratios of CD44+NK1.1+, CD122+, CD69+ and DX5+ cells were significantly decreased(P<0.05).The experiment of mixed bone marrow chimerism showed that the number of iNKT cells from the bone marrow cells of the HDAC3KO mice was significantly decreased compared with the bone marrow cells of the B6.SJL mice(P<0.05),and the ratio of CD44+NK1.1+ cells in the iNKT cells from the bone marrow cells of the HDAC3KO mice was significantly lower than that of the iNKT cells from the B6.SJL mice (P<0.05).The results of intracellular staining and ELISA showed that the levels of IFN-γ and IL-4 in the iNKT cells and serum of the HDAC3KO mice were significantly decreased compared with the WT mice(P<0.05). Conclusion: HDAC3 deficiency results in the decrease of the number of iNKT cells and the blocking of development and maturation of iNKT cells by an endogenous pathway.In addition, HDAC3 deficiency results in the significant reduction of cytokine production in the iNKT cells. All the results indicate that HDAC3 plays an important role in the regulation of iNKT cell development and function.

Key words: histone deacetylase 3, invariant nature killer T cells, cell development, cell function

CLC Number:

R392.11

ZHENG Quanhui, LEI Bing, YUAN Hongru, MA Jiannan, LIU Zhaoji, ZHANG Jun, LIU Yibo, ZHANG Bing, ZHANG Aihong, ZHENG Aihua, ZHANG Ying, LI Huiting, TIAN Feng. Regulatoy effects of HDAC3 on development and function of iNKT cells[J].Journal of Jilin University(Medicine Edition), 2020, 46(02): 205-213.

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Regulatoy effects of HDAC3 on development and function of iNKT cells

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