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Updated: Jul 12, 2025

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
Published on: May 10, 2022
CD226 maintains regulatory T cell phenotype stability and metabolism by the mTOR/Myc pathway under inflammatory
Jingchang Ma1, Wei Hu2, Yitian Liu1
1Department of Immunology, Fourth Military Medical University, #169 West Changle Road, Xi'an, Shaanxi 710032, China.
Abstract:
Regulatory T (Treg) cells exhibit immunosuppressive phenotypes and particular metabolic patterns with certain degrees of plasticity. Previous studies of the effects of the co-stimulatory molecule CD226 on Treg cells are controversial. Here, we show that CD226 primarily maintains the Treg cell stability and metabolism phenotype under inflammatory conditions. Conditional deletion of CD226 within Foxp3+ cells exacerbates symptoms in murine graft versus host disease models. Treg cell-specific deletion of CD226 increases the Treg cell percentage in immune organs but weakens their immunosuppressive function with a T helper 1-like phenotype conversion under inflammation. CD226-deficient Treg cells exhibit reduced oxidative phosphorylation and increased glycolysis rates, which are regulated by the adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/myelocytomatosis oncogene (Myc) pathway, and inhibition of Myc signaling restores the impaired functions of CD226-deficient Treg cells in an inflammatory disease model of colitis. This study reveals an Myc-mediated CD226 regulation of Treg cell phenotypic stability and metabolism, providing potential therapeutic strategies for targeted interventions of Treg cell-specific CD226 in inflammatory diseases.
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