TIGIT predominantly regulates the immune response via regulatory T cells
| Autor: | Sema Kurtulus, Ana C. Anderson, Shin Foong Ngiow, Kaori Sakuishi, Vijay K. Kuchroo, Nicole Joller, Michele W.L. Teng, Dewar J. Tan, Mark J. Smyth |
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| Rok vydání: | 2015 |
| Předmět: |
Virus genetics
Adoptive cell transfer CD96 T cell Melanoma Experimental chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Immunophenotyping Mice Immune system Lymphocytes Tumor-Infiltrating TIGIT medicine Animals Receptors Immunologic Receptor Hepatitis A Virus Cellular Receptor 2 Mice Knockout Mice Inbred BALB C General Medicine Adoptive Transfer 3. Good health Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic Mice Inbred C57BL medicine.anatomical_structure Immunology Colonic Neoplasms Cancer research Receptors Virus Female Receptors Chemokine CD8 T-Lymphocytes Cytotoxic Transcription Factors Research Article |
| Zdroj: | The Journal of clinical investigation. 125(11) |
| ISSN: | 1558-8238 |
| Popis: | Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation of these receptors on effector T cells terminates T cell responses, while their expression on Tregs promotes their suppressor function. Understanding the function of coinhibitory receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory receptors are currently at the forefront of treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that is found on the surface of a variety of lymphoid cells, and its role in immune regulation is just beginning to be elucidated. We examined TIGIT-mediated immune regulation in different murine cancer models and determined that TIGIT marks the most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT signaling in Tregs directs their phenotype and that TIGIT primarily suppresses antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings provide mechanistic insight into how TIGIT regulates immune responses in chronic disease settings. |
| Databáze: | OpenAIRE |
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