Year: 2023
Type: article
Abstract: Treg suppressive mechanisms limit immune reactivityTregs are a specialized subset of CD4 + T cells characterized by the expression of the master transcription factor, Foxp3, which orchestrates Treg development and function.Rather than inducing cytolytic or proinflammatory immune cell function, Tregs suppress immune responses under steady state and upon inflammatory challenges, thereby preventing tissue damage and other pathologies.To mediate these effects, Tregs utilize multiple suppressive mechanisms, including deprivation of IL-2 (1-3), secretion of inhibitory cytokines IL-10 and TGF-β (1, 3), and production of cytolytic granzymes (1, 3).Cell-cell contact also plays a crucial role in Treg-mediated suppression.For instance, Tregs express high levels of several coinhibitory receptors (e.g., TIGIT, PD-1, CTLA-4), which trigger suppressive signaling or removal of key stimulatory molecules expressed on DCs to limit conventional T cell (Tconv) activation (1, 3-5).Although Tregs strongly adhere to DCs via interactions between LFA-1 and ICAM-1 (6-8), it remains poorly understood whether and how Foxp3 orchestrates Treg contact-dependent suppressive function.Exploring the molecular basis may uncover therapies for tuning Tconv responses in autoimmune or allergic disease, organ or tissue transplantation, and cancer.In this issue of the JCI, Wang and authors report a Foxp3-regulated mechanism that facilitates strong Treg-DC interaction, which is associated with potent immunosuppression in murine models of autoimmunity, inflammation, and cancer (9) (Figure 1).
DOI: 10.1172/jci172986
Institution: St. Jude Children's Research Hospital
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1980380190, G4597687758, Nutrient sensing and lysosomal signaling in regulatory T cells and immune tolerance, G6247008096, G9000213926, Transcriptional and metabolic heterogeneity in T cell differentiation, Regulation of T cell memory in tissue immunity, Enabling immunotherapy for high-risk Group 3 medulloblastoma via systems immunology
OpenAlex ID: W4389725564