Spatiotemporal regulation of peripheral T cell tolerance

• 成果类型: Review
• 署名作者: Brown, Chrysothemis C.; Rudensky, Alexander Y.
• 署名单位: Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9869
• DOI: 10.1126/science.adg6425
• 发表日期: 2023-05-05
• 页码: 472-478
• 关键词: dendritic cells; differentiation; autoimmunity; metabolites; induction; antigens; inhibition; immunity; absence; LIFE

摘要

The incomplete removal of T cells that are reactive against self-proteins during their differentiation in the thymus requires mechanisms of tolerance that prevent their effector function within the periphery. A further challenge is imposed by the need to establish tolerance to the holobiont self, which comprises a highly complex community of commensal microorganisms. Here, we review recent advances in the investigation of peripheral T cell tolerance, focusing on new insights into mechanisms of tolerance to the gut microbiota, including tolerogenic antigen-presenting cell types and immunomodulatory lymphocytes, and their layered ontogeny that underlies developmental windows for establishing intestinal tolerance. While emphasizing the intestine as a model tissue for studying peripheral T cell tolerance, we highlight overlapping and distinct pathways that underlie tolerance to self-antigens versus commensal antigens within a broader framework for immune tolerance.