Inhibition of Lck/Fyn kinase activity promotes the differentiation of induced Treg cells through AKT/mTOR pathway.
Int Immunopharmacol
; 134: 112237, 2024 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-38744170
ABSTRACT
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 TGFß. 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Diferenciação Celular
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Linfócitos T Reguladores
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Proteína Tirosina Quinase p56(lck) Linfócito-Específica
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China