{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:18Z","timestamp":1785411378190,"version":"3.56.0"},"reference-count":160,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\/4504-2022"],"award-info":[{"award-number":["RGPIN\/4504-2022"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RGPIN\/4504-2022"],"award-info":[{"award-number":["RGPIN\/4504-2022"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Semaphorins are a large family of proteins originally identified for their roles in axon guidance during neural development. Recent findings have established the importance of semaphorins members in modulating diverse immune responses of T cells in vitro and in vivo. Class 3 semaphorins, typified by Sema3A, signal through Neuropilin-1 and Plexin-A receptors in an activation-dependent manner, suppressing effector proliferation while promoting regulatory T cell stability and shaping cytokine profiles in autoimmunity and cancer. Sema3E and Sema3F similarly fine-tune host defense and inflammation by directing Th1\/Th17 responses or restraining aberrant chemotaxis. Class 4 members, such as Sema4A and Sema4D, engage Plexin-B1, Plexin-D1, and CD72 to deliver both \u201cforward\u201d co-stimulatory and \u201creverse\u201d signals: they amplify CD4+ and CD8+ effector functions, support T helper-B cell crosstalk, and influence tumor immunity via receptor shedding and bidirectional signaling. Finally, although less well defined, class 7 Sema7A operates indirectly\u2014through APCs and Tregs\u2014to regulate inflammatory recall responses and Th1\/Th17 driven pathology. Together, these semaphorin-mediated pathways underscore a complex, context-dependent network that balances protective immunity against immunopathology, offering novel therapeutic targets in autoimmunity, infection, and cancer.<\/jats:p>","DOI":"10.3390\/cells15121047","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T02:32:46Z","timestamp":1780885966000},"page":"1047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diverse Roles of Semaphorins on T Cell Activation, Differentiation, Migration, and Effector Functions"],"prefix":"10.3390","volume":"15","author":[{"given":"Heqing","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelilah S.","family":"Gounni","sequence":"additional","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-1073","authenticated-orcid":false,"given":"Ruey-Chyi","family":"Su","sequence":"additional","affiliation":[{"name":"National Sexually Transmitted Blood Borne Infection Laboratory Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6791-0031","authenticated-orcid":false,"given":"Sam K. 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