Inhibition of Lck/Fyn kinase activity promotes the differentiation of induced Treg cells through AKT/mTOR pathway.

Autor: Qin Z; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China., Hou P; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China., Lin H; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China., Chen M; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China., Wang R; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China., Xu T; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: xutao25@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Jun 15; Vol. 134, pp. 112237. Date of Electronic Publication: 2024 May 13.
DOI: 10.1016/j.intimp.2024.112237
Abstrakt: Regulatory T (Treg) cells are indispensable in maintaining the immune homeostasis and preventing autoimmune diseases. Regulatory T (Treg) cells include thymus derived Treg cells (tTregs) and peripherally induced Treg cells (iTreg), which are differentiated from antigen stimulated CD4 + naïve T cells in presence of TGFβ. tTregs are quite stable, and more immune suppressive, while iTreg cells are less stable, and are prone to differentiate into inflammatory T cells. Therefore, identification of small molecules that could promote the differentiation of iTreg cells is an attractive strategy for autoimmune diseases. Inhibition of AKT/mTOR pathway promotes their differentiation. Whether inhibition of Lck/Fyn kinase activity (upstream of AKT/mTOR pathway) can be used to promote the differentiation of iTreg cells has not been determined. Here, we showed that Srci1, a small molecular inhibitor of Lck/Fyn, promoted the differentiation of FOXP3 + iTreg cells. Srci1 treatment resulted in inhibition of phosphorylation of key components of AKT/mTOR pathway, including mTOR, p70 S6K, 4EBP1, and promoted the expression of Foxp3 and its target genes, thereby promoted differentiation of in vitro iTreg cells. Srci1 treated iTreg cells showed more similar gene expression profile to that of tTreg cells. Our results thus suggest that inhibition of Lck/Fyn kinase activity can promote the differentiation of iTreg cells, and may have implication in autoimmune diseases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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