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Effect of SHP2 deficiency on gene expression in stimulated Treg cells

ABSTRACT: Regulatory CD4+ T cells (Tregs) play a critical role in immune regulation, and their dysfunction can lead to autoimmunity. However, the molecular mechanisms regulating Treg function remain incompletely understood. The Src homology region 2 domain-containing phosphatase 2 (SHP-2) has been implicated in lymphocyte development and activation by modulating signaling pathways downstream of co-stimulatory and cytokine receptors in T cells. To investigate the role of SHP-2 in Tregs, we generated Treg-specific SHP-2--deficient mice. Under steady-state conditions, these mice exhibited normal T cell populations without overt disease. However, SHP-2--deficient Tregs displayed enhanced proliferation and suppressive capacity in in vitro or in vivo assays, accompanied by altered surface marker expression. To further assess their functional impact, we employed three clinically relevant models, i.e., Dextran Sulfate Sodium (DSS)-induced colitis, experimental autoimmune encephalomyelitis (EAE), and B16 melanoma. Ptpn11fl/fl Foxp3Cre mice showed attenuated disease severity in both colitis and EAE, but accelerated tumor progression in the melanoma model. These findings align with the enhanced immunosuppressive activity observed in suppression assays. Mechanistically, SHP-2 deficiency altered IL-2R--STAT5 signaling in Tregs, providing insight into its regulatory role. Collectively, our study demonstrates that SHP-2 modulates Treg function and reveals its therapeutic potential for targeted immune modulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE345386 | GEO | 2026/09/02

REPOSITORIES: GEO

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