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Immunity ; 40(4): 569-81, 2014 Apr 17.
Article in English | MEDLINE | ID: mdl-24745333

ABSTRACT

Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.


Subject(s)
Fibrinogen/metabolism , Receptors, Immunologic/metabolism , Respiratory Hypersensitivity/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Cell Proliferation , Cells, Cultured , Cytokines/metabolism , Eosinophils/immunology , Fibrinogen/genetics , Fibrinogen/immunology , Forkhead Transcription Factors/metabolism , Gene Expression Profiling , Gene Expression Regulation , Immunosuppression Therapy , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Receptors, Immunologic/genetics , Receptors, Immunologic/immunology , Th1-Th2 Balance
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