The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells
| Autor: | Xin Yu, Hilary Clark, Kristin Harden, Eugene Chiang, Canio J. Refino, Bryan Irving, Lino C. Gonzalez, Dan L. Eaton, Michelle Francesco, Jane L. Grogan, Irene Tom, Sinisa Ivelja |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD96
CD226 T cell T-Lymphocytes Immunology Molecular Sequence Data Down-Regulation CHO Cells Cell Communication Biology Mice Cricetulus TIGIT Cricetinae medicine Immune Tolerance Immunology and Allergy Animals Humans CD155 Amino Acid Sequence Receptors Immunologic Cells Cultured Interleukin-12 Subunit p40 Interleukin Membrane Proteins Cell Differentiation Dendritic Cells Molecular biology Interleukin-10 Mice Inbred C57BL Interleukin 10 medicine.anatomical_structure biology.protein Receptors Virus Immunologic Memory Sequence Alignment Poliovirus Receptor Protein Binding |
| Zdroj: | Nature immunology. 10(1) |
| ISSN: | 1529-2916 |
| Popis: | Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells. |
| Databáze: | OpenAIRE |
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