{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:36:28Z","timestamp":1776836188471,"version":"3.51.2"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to investigate the role of myofiber-specific TGF-\u03b2 signaling in the development of muscle inflammation by modulating Treg-cell-mediated macrophage efferocytosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CTX-induced muscle injury was performed in the tibialis anterior (TA) of control (TGF-\u03b2r2\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      ) and transgenic mice with skeletal muscle-specific deletion of TGF-\u03b2 receptor 2 (SM TGF-\u03b2r2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ). Gene levels of regulatory T cell (Treg) activation markers and inflammatory mediators produced by macrophages or Tregs were assessed using qRT-PCR. Intramuscular infiltration of Tregs and macrophages, as well macrophage phenotypes, efferocytic function, and associated signaling molecules, were evaluated using hematoxylin and eosin (HE) staining, immunofluorescence, immunoblotting and FACS analysis. The correlation of myofibers with Tregs-mediated macrophage efferocytosis were addressed under an\n                      <jats:italic>in vitro<\/jats:italic>\n                      co-culture system, which including Tregs, macrophages, and the differentiated myogenic precursor cells (MPC-myotubes) isolated from control or SM TGF-\u03b2r2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Apoptotic cells were generated by UV irradiation prior to transfer into inflamed muscle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Deficiency in muscle TGF-\u03b2 signaling resulted in more severe muscle inflammation, characterized by an increased number of M1 macrophages and a decreased number of M2 macrophages. Notably, the absence of muscle TGF-\u03b2 signaling impaired the efferocytic capacity of macrophages and reduced the proportion of Tregs in inflamed muscle. Further, we monitored that activation of intrinsic TGF-\u03b2 signaling suppresses myofiber IL-6 production, which in turn impacted on IL-13 production from Tregs accumulated in damaged muscle. This ultimately facilitates IL-10-STAT3-Vav1-mediated macrophage efferocytosis in inflamed muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings establish a link between muscle-specific TGF-\u03b2 signaling, myokine IL-6, Tregs derived IL-13 and macrophage efferocytosis in inflamed muscle. These results suggest that therapeutic targeting of this axis may hold promise for promoting muscle regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1810106","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:37:01Z","timestamp":1776832621000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regenerating myofiber with activating of TGF-\u03b2 signaling contributes to macrophage efferocytosis through enhancing Tregs response in inflamed muscle"],"prefix":"10.3389","volume":"17","author":[{"given":"HaiQiang","family":"Lan","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"QiSen","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JingWen","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiJie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, 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