{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:14:50Z","timestamp":1783401290918,"version":"3.54.6"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"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>Objective<\/jats:title>\n                    <jats:p>T cell\u2013mediated rejection (TCMR) remains a major barrier to long-term kidney allograft survival, driven by recipient immune responses against donor antigens. A comprehensive understanding of the cellular and molecular mechanisms underlying TCMR is essential for developing novel diagnostic and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated two public single-cell RNA sequencing datasets (GSE145927 and E-MTAB-12051) to construct a comprehensive single-cell atlas of kidney allograft biopsies. Unsupervised clustering, functional scoring, trajectory inference, gene regulatory network analysis, and cell\u2013cell communication analysis were performed. Key findings were validated in a murine TCMR model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the single TCMR sample analyzed, we observed several cell populations that were enriched and may be associated with TCMR. An NQO1\n                      <jats:sup>+<\/jats:sup>\n                      NDUFS4\n                      <jats:sup>+<\/jats:sup>\n                      proximal tubular subset exhibited marked activation of oxidative phosphorylation and fatty acid metabolism, consistent with metabolic remodeling under inflammatory stress. An S100A8\n                      <jats:sup>+<\/jats:sup>\n                      macrophage subset displayed a pro-inflammatory phenotype and actively recruited CD8\n                      <jats:sup>+<\/jats:sup>\n                      T and NKT cells via chemokine signaling. A CCL4L2\n                      <jats:sup>+<\/jats:sup>\n                      NKT subset exacerbated rejection by enhancing immune recruitment and cytotoxic functions. These innate immune cells formed extensive communication networks with adaptive immune cells through chemokine (CXCL10-CXCR3) and inflammatory (TNF-TNFRSF1A\/B) axes, suggesting a potential molecular basis for innate-adaptive immune crosstalk. Additionally, a DUSP1\n                      <jats:sup>+<\/jats:sup>\n                      effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T subset was selectively enriched in TCMR and showed robust T cell receptor activation, and may be associated with graft injury potentially through the B2M\/MHC class I axis. In a murine model, we observed upregulation and functional dependence of Dusp1\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, consistent with the findings from the single human TCMR case.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This hypothesis-generating study, based on a single TCMR case, provides a single-cell atlas of the TCMR immune microenvironment and suggests several subsets and pathways that may be involved. Our findings suggest that innate immune cells may initiate and amplify adaptive responses through chemokine and inflammatory networks, providing new insights into the potential role of innate immunity in allograft injury. The DUSP1\n                      <jats:sup>+<\/jats:sup>\n                      effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell\u2013B2M\/MHC class I axis was observed in this single case and may represent a candidate for further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1827224","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:23:29Z","timestamp":1783398209000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Innate-immune crosstalk orchestrates T cell-mediated rejection in kidney transplants"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuyun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First People\u2019s Hospital of Nanning","place":["Nanning, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Pathology Department, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanmiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Basic Science, YuanDong Life California Ivy Research Institute","place":["West 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