{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:27:31Z","timestamp":1786955251044,"version":"build-2736575974"},"reference-count":94,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Regulatory T cells (Tregs) play a pivotal role in maintaining immune homeostasis by exerting precise control over immune activation, suppressing excessive responses, and facilitating tissue repair. These specialized CD4+ T cells, characterized by FOXP3 expression, function as key regulators that prevent pathogen-directed immune responses from progressing to deleterious autoimmunity or chronic inflammation. Tregs mediate suppression via secretion of cytokines such as IL-10 and TGF-\u03b2, metabolic disruption, and direct modulation of effector immune cells, thereby maintaining equilibrium between protective immunity and peripheral tolerance. Both thymically derived natural Tregs (nTregs) and peripherally induced Tregs (pTregs) exhibit phenotypic plasticity, adapting to diverse inflammatory milieus and tissue microenvironments through an array of suppressive mechanisms that orchestrate immune regulation and facilitate tissue repair. This functional heterogeneity manifests across lymphoid and non-lymphoid tissues, wherein Tregs dynamically adapt to distinct microenvironments to mount tailored responses to infection, tissue injury, and inflammatory insults. Conversely, Tregs may promote disease progression in malignancies and persistent infections by attenuating antitumor and antimicrobial immune effector responses. Treg activity is essential for averting autoimmune pathologies, tempering inflammatory cascades, and fostering tissue regeneration, thereby rendering them indispensable for upholding both systemic and tissue-specific immune homeostasis. Elucidation of Treg immunobiology unveils substantial therapeutic prospects across a diverse array of pathologies; targeted modulation of Treg frequency and functionality offers promise for ameliorating autoimmunity, mitigating transplant rejection, and combating malignancy. This narrative review delineates the multifaceted roles of Tregs in immune homeostasis, elucidates emerging insights into their mechanistic underpinnings, and evaluates prospective applications in next-generation immunotherapeutic interventions.<\/jats:p>","DOI":"10.3390\/cells15161462","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:05:41Z","timestamp":1786953941000},"page":"1462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulatory T Cell (Treg): Central Orchestrator of Immune Homeostasis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-9237","authenticated-orcid":false,"given":"Md. Abdus","family":"Salam","sequence":"first","affiliation":[{"name":"Department of Microbiology, North Bengal Medical College, Sirajganj 6700, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6086-5159","authenticated-orcid":false,"given":"Md. Yusuf","family":"Al-Amin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7072-3226","authenticated-orcid":false,"given":"Kasireddy","family":"Sudarshan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Whalen","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1728-0306","authenticated-orcid":false,"given":"Campbell","family":"Gideon","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabella","family":"Cordovez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arneth, B. 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