Insulin Receptor Substrate 1 Signaling Inhibits Foxp3 Expression and Suppressive Functions in Treg Cells through the mTORC1 Pathway

被引：1

作者：

Lee, Woo Ho ^{[1
]}

Kim, Ga Eul ^{[1
]}

Hong, Kyung Jin ^{[1
]}

Kim, Hyeong Su ^{[1
]}

Lee, Gap Ryol ^{[1
]}

机构：

[1] Sogang Univ, Dept Life Sci, 35 Baekbeom Ro, Seoul 04107, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

IRS1; Treg cell; Foxp3; mTORC1; colitis; REGULATORY T-CELLS; EFFECTOR; TRANSCRIPTION; GENE; DIFFERENTIATION; TARGET;

D O I：

10.3390/ijms24032551

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Regulatory T (Treg) cells play an important role in immune homeostasis by inhibiting cells within the innate and adaptive immune systems; therefore, the stability and immunosuppressive function of Treg cells need to be maintained. In this study, we found that the expression of insulin receptor substrate 1 (IRS1) by Treg cells was lower than that by conventional CD4 T cells. IRS1-overexpressing Treg cells showed the downregulated expression of FOXP3, as well as Treg signature markers CD25 and CTLA4. IRS1-overexpressing Treg cells also showed diminished immunosuppressive functions in an in vitro suppression assay. Moreover, IRS1-overexpressing Treg cells were unable to suppress the pathogenic effects of conventional T cells in a transfer-induced colitis model. IRS1 activated the mTORC1 signaling pathway, a negative regulator of Treg cells. Moreover, IRS1 destabilized Treg cells by upregulating the expression of IFN-gamma and Glut1. Thus, IRS1 acts as a negative regulator of Treg cells by downregulating the expression of FOXP3 and disrupting stability.

引用

页数：17

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