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However, the role of specific FRC subsets in controlling alloimmune responses remains to be studied. Single-cell RNA sequencing (scRNA-Seq) of naive and draining LNs (DLNs) of heart-transplanted mice and human LNs revealed a specific subset of CXCL12\n                    <jats:sup>hi<\/jats:sup>\n                    FRCs that expressed high levels of lymphotoxin-\u03b2 receptor (LT\u03b2R) and are enriched in the expression of immunoregulatory genes. CXCL12\n                    <jats:sup>hi<\/jats:sup>\n                    FRCs had high expression of CCL19, CCL21, indoleamine 2,3-dioxygenase (IDO), IL-10, and TGF-\u03b21. Adoptive transfer of ex vivo\u2013expanded FRCs resulted in their homing to LNs and induced immunosuppressive environments in DLNs to promote heart allograft acceptance. Genetic deletion of\n                    <jats:italic>LT<\/jats:italic>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:italic>R<\/jats:italic>\n                    and\n                    <jats:italic>Cxcl12<\/jats:italic>\n                    in FRCs increased alloreactivity, abrogating the effect of costimulatory blockade in prolonging heart allograft survival. As compared with WT recipients, CXCL12\n                    <jats:sup>+<\/jats:sup>\n                    FRC\u2013deficient recipients exhibited increased differentiation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells into Th1 cells. Nano delivery of CXCL12 to DLNs improved allograft survival in heart-transplanted mice. Our study highlights the importance of DLN CXCL12\n                    <jats:sup>hi<\/jats:sup>\n                    FRCs in promoting transplant tolerance.\n                  <\/jats:p>","DOI":"10.1172\/jci182709","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T07:59:44Z","timestamp":1746086384000},"source":"Crossref","is-referenced-by-count":11,"title":["CXCL12+ fibroblastic reticular cells in lymph nodes facilitate immune tolerance by regulating T cell\u2013mediated alloimmunity"],"prefix":"10.1172","volume":"135","author":[{"given":"Yuta","family":"Yamamura","sequence":"first","affiliation":[{"name":"Transplantation Research Center and"},{"name":"Renal Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Sabiu","sequence":"additional","affiliation":[{"name":"Transplantation Research Center and"},{"name":"Renal 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