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Advances in mechanoimmunology show that T-cell behavior is tightly shaped by the physical properties of their environment, including stiffness, viscoelasticity, ligand arrangement, and tissue topography. T-cell activation depends not only on biochemical signals but also on forces transmitted through the T-cell receptor, coreceptors, and mechanosensitive ion channels, which converge on the cytoskeleton to regulate signaling and effector function. When these mechanical interactions are disrupted, as in cancer, autoimmune diseases, or aging, T-cell function is impaired. Despite recent progress, T-cell mechanobiology remains partially understood, limited by challenges in measuring forces at relevant spatial and temporal scales. Incorporating biophysical principles into the design of immunotherapies may enhance treatment efficacy, specificity, and safety. This review summarizes emerging concepts in T-cell mechanobiology and outlines key challenges and future directions toward integrating mechanical and biochemical regulation of adaptive immunity.<\/jats:p>","DOI":"10.1083\/jcb.202601058","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:21:19Z","timestamp":1777011679000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["T-cell mechanobiology: How molecular forces shape immune function"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9719-3114","authenticated-orcid":true,"given":"Judith","family":"Zubia-Aranburu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01aj84f44","id-type":"ROR","asserted-by":"publisher"}],"name":"Interdisciplinary Nanoscience Center (iNANO), Aarhus University 1 , Aarhus,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-6065","authenticated-orcid":true,"given":"Lingxiao","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01aj84f44","id-type":"ROR","asserted-by":"publisher"}],"name":"Interdisciplinary Nanoscience Center (iNANO), Aarhus University 1 , Aarhus,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2025-2171","authenticated-orcid":true,"given":"Mingdong","family":"Dong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01aj84f44","id-type":"ROR","asserted-by":"publisher"}],"name":"Interdisciplinary Nanoscience Center (iNANO), Aarhus University 1 , Aarhus,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"2026052109394096400_bib1","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/s41577-020-0307-4","article-title":"Clonal expansion of innate and adaptive lymphocytes","volume":"20","author":"Adams","year":"2020","journal-title":"Nat. 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