The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhi...The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhibit heterogeneous phenotypes under inflammatory conditions.However,the interplay between inflammation and Treg cell suppressive activity still remains elusive.Here,we utilized singlecell RNA sequencing to investigate how human Treg cells respond to the pro-inflammatory cytokine interleukin-6(IL-6).We observed that Treg cells divided into two subpopulations after IL-6 stimulation.TIGITàunstable Treg cells lost FOXP3 expression and gained an effector-like T cell phenotype,whereas TIGIT+Treg cells retained robust suppressive function.Single cell transcriptome analysis revealed a spectrum of cellular states of IL-6-stimulated Treg cells and how cytochrome P450 family 1 subfamily A member 1(CYP1A1)is a crucial regulator of Treg cell suppressive capability and stability.CYP1A1-deficient human Treg cells developed a Th17-like phenotype after IL-6 stimulation.Our findings implicate CYP1A1 as a previously unidentified regulator of Treg cells that may have target potential for clinical application for biotherapies.展开更多
基金supported by grants from the National Natural Science Foundation of China (81830051, 31525008, 31670911, 31800744 and 31961133011)Shanghai Academic Research Leader (16XD1403800)+2 种基金Shenzhen Municipal Government of China (JCYJ20170817145428361)Shanghai Jiao Tong University (SJTU)The Chinese University of Hong Kong (CUHK) Joint Research Collaboration Fundthe Fundamental Research Funds for Central Universities and the Gusu innovation and entrepreneurship leader talent program。
文摘The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhibit heterogeneous phenotypes under inflammatory conditions.However,the interplay between inflammation and Treg cell suppressive activity still remains elusive.Here,we utilized singlecell RNA sequencing to investigate how human Treg cells respond to the pro-inflammatory cytokine interleukin-6(IL-6).We observed that Treg cells divided into two subpopulations after IL-6 stimulation.TIGITàunstable Treg cells lost FOXP3 expression and gained an effector-like T cell phenotype,whereas TIGIT+Treg cells retained robust suppressive function.Single cell transcriptome analysis revealed a spectrum of cellular states of IL-6-stimulated Treg cells and how cytochrome P450 family 1 subfamily A member 1(CYP1A1)is a crucial regulator of Treg cell suppressive capability and stability.CYP1A1-deficient human Treg cells developed a Th17-like phenotype after IL-6 stimulation.Our findings implicate CYP1A1 as a previously unidentified regulator of Treg cells that may have target potential for clinical application for biotherapies.
