DNAM-1 regulates the proliferation and function of T regulatory type 1 cells via the IL-2/STAT5 pathway.
10.12122/j.issn.1673-4254.2022.09.03
- Author:
Ning WANG
1
;
Yi Han WANG
2
;
Peng Tao JIANG
1
;
Ming Hua LÜ
1
;
Zhi Fang HU
1
;
Xi XU
1
Author Information
1. Institute of Basic Medicine, Xi'an Medical University, Xi'an 710021, China.
2. Department of General Practitioners, Xi'an Medical University, Xi'an 710021, China.
- Publication Type:Journal Article
- Keywords:
DNAM-1;
STAT5;
interleukin-10;
interleukin-2;
type Ⅰ regulatory T cells
- MeSH:
Animals;
Antigens, Differentiation, T-Lymphocyte;
CD28 Antigens/metabolism*;
Cell Proliferation;
Cells, Cultured;
Interleukin-10;
Interleukin-2/metabolism*;
Mice;
RNA, Messenger;
STAT5 Transcription Factor/metabolism*;
T-Lymphocytes, Regulatory
- From:
Journal of Southern Medical University
2022;42(9):1288-1295
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of DNAM-1 in the activation, proliferation and function of type Ⅰ regulatory T cells (Tr1 cells).
METHODS:Anti-CD3/CD28 antibodies were used to stimulate mouse T cells derived from the spleen of wild-type (WT) mice, and the expression level of DNAM-1 in resting and activated Tr1 cells was evaluated with flow cytometry. Na?ve CD4+ T cells isolated by magnetic cell sorting from the spleens of WT mice and DNAM-1 knockout (KO) mice were cultured in Tr1 polarizing conditions for 3 days, after which CD25 and CD69 expressions were measured using flow cytometry. The induced Tr1 cells were labelled with CFSE and cultured in the presence of anti-CD/CD28 antibodies for 3 days, and their proliferative activity was analyzed. The expressions of IL-10 and p-STAT5 in DNAM-1-deficient Tr1 cells were detected before and after IL-2 stimulation.
RESULTS:The expression level of DNAM-1 was significantly upregulated in CD4+ T cells and Tr1 cells after stimulation with anti-CD3/CD28 antibodies (P < 0.05). DNAM-1 knockout did not cause significant changes in the number or proportion of Tr1 cells, but but significantly increased the expression levels of the activation markers CD69 and CD25 (P < 0.05). Compared with WT Tr1 cells, DNAM-1-deficient Tr1 cells exhibited reduced proliferative activity in vitro (P < 0.05) with downregulated IL-10 production (P < 0.05) and decreased expressions of Il-10 and Gzmb mRNA (P < 0.05). In DNAM-1-deficient Tr1 cells, IL-2 stimulation significantly reduced IL-10 secretion level and the expression of p-STAT5 as compared with WT Tr1 cells.
CONCLUSION:DNAM-1 participate in the activation and proliferation of Tr1 cells and affect the biological functions of Tr1 cells through the IL-2/STAT5 pathway.
