Tissue regulatory T cells: regulatory chameleons

• Published in: Nature reviews. Immunology Vol. 21; no. 9; pp. 597 - 611
• Main Authors: Muñoz-Rojas, Andrés R., Mathis, Diane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2021; Nature Publishing Group
• Subjects: 631/250/1619; 631/250/256; Animals; Biomedical and Life Sciences; Biomedicine; CD4 antigen; Cell differentiation; Cell proliferation; Cellular control mechanisms; Female; Foxp3 protein; Health aspects; Homeostasis; Homeostasis - immunology; Humans; Immunology; Immunoregulation; Immunosurveillance; Intra-Abdominal Fat - cytology; Intra-Abdominal Fat - immunology; Lymphocytes T; Lymphoid tissue; Male; Metabolism; Mice; Models, Immunological; Muscle, Skeletal - cytology; Muscle, Skeletal - immunology; Phenotypes; Physiological aspects; Progenitor cells; Receptors, Antigen, T-Cell - immunology; Review Article; Skin - cytology; Skin - immunology; Stem cells; Suppressor cells; Survival factor; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - physiology; Tissues; Transcription; Transcriptome; Transcriptomes; United States
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/s41577-021-00519-w

The FOXP3 + CD4 + regulatory T (T reg ) cells located in non-lymphoid tissues differ in phenotype and function from their lymphoid organ counterparts. Tissue T reg cells have distinct transcriptomes, T cell receptor repertoires and growth and survival factor dependencies that arm them to survive and operate in their home tissue. Their functions extend beyond immune surveillance to tissue homeostasis, including regulation of local and systemic metabolism, promotion of tissue repair and regeneration, and control of the proliferation, differentiation and fate of non-lymphoid cell progenitors. T reg cells in diverse tissues share a common FOXP3 + CD4 + precursor located within lymphoid organs. This precursor undergoes definitive specialization once in the home tissue, following a multilayered array of common and tissue-distinct transcriptional programmes. Our deepening knowledge of tissue T reg cell biology will inform ongoing attempts to harness T reg cells for precision immunotherapeutics. Regulatory T cells present in non-lymphoid tissues such as the skin, fat and muscle are distinct from their counterparts in lymphoid tissues. Their functions extend beyond immune surveillance to the control of local metabolism, tissue repair and tissue cell progenitors, as discussed in this Review.