{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:44:05Z","timestamp":1777013045191,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372565"],"award-info":[{"award-number":["82372565"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172537"],"award-info":[{"award-number":["82172537"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002376"],"award-info":[{"award-number":["82002376"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic psychological stress drives neuroimmune crosstalk and accelerates atherosclerosis progression. Physical exercise confers broad health benefits and is associated with reduced inflammation. However, the exercise\u2010mediated factors and mechanisms that mitigate stress\u2010induced vascular inflammation remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Chronic restraint stress (CRS) and voluntary exercise models were established to investigate the role of exercise in neuroimmune crosstalk. RNA sequencing identified kinesin family member 4 (Kif4) as a key gene associated with the attenuation of stress\u2010induced inflammatory responses in peripheral blood monocytes following exercise. Combined co\u2010immunoprecipitation\u2013mass spectrometry and membrane proteomics identified T cell\u2010interacting activating receptors on myeloid cell 1 (TARM1) as the Kif4 cargo. The function of TARM1 was validated using an immobilized TARM1\u2010Fc fusion protein. Brain\u2010derived neurotrophic factor (BDNF), a key effector during exercise and stress, regulated the Kif4\u2013TARM1 axis using recombinant BDNF (rBDNF) and the TrkB inhibitor ANA\u201012. Finally, exercise\u2010mediated effects and mechanisms were examined in atherosclerotic CRS\u2010exposed mouse models and in patients with coronary artery disease (CAD) experiencing high psychological stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Physical exercise alleviated stress\u2010induced neuroimmune crosstalk, reduced the proinflammatory CD11b\n                      <jats:sup>+<\/jats:sup>\n                      Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      monocyte phenotype, and suppressed M1 macrophage polarization. Kif4 knockdown mitigated proinflammatory responses in peripheral blood monocytes and BMDMs in the CRS model mice. Mechanistically, kinesin Kif4 facilitates microtubule\u2010dependent transport of TARM1 to the plasma membrane, thereby promoting macrophage inflammatory responses and enhancing monocyte\u2012endothelial cell adhesion. Conversely, neurogenic BDNF, regulated by exercise and stress, activated the TrkB receptor in monocytes\/macrophages and inhibited the p\u2010STAT3\/Kif4\/TARM1 signalling pathway. Furthermore, in both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress\u2010induced inflammation via the BDNF\u2013Kif4\u2013TARM1 axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Physical exercise alleviates stress\u2010induced neuroimmune crosstalk through the BDNF\u2013Kif4\u2013TARM1 axis, revealing a novel neuroimmune\u2010mediated brain\u2013heart axis that supports exercise\u2010based therapeutic strategies for psychogenic CAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Chronic psychological stress drives systemic inflammation through neuroimmune mechanisms, thereby accelerating the progression of coronary artery disease (CAD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Physical exercise alleviates stress\u2010induced neuroimmune crosstalk, partly by suppressing proinflammatory responses in monocytes\/macrophages.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study provides novel insights into exercise\u2010regulated neuroimmune mechanisms involving the monocyte BDNF\u2013Kif4\u2013TARM1 axis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress\u2010induced inflammation via the BDNF\u2013Kif4\u2013TARM1 axis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n          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