{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:03:57Z","timestamp":1790089437696,"version":"4.0.1"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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:p>\n                    Graft-versus-host disease (GVHD) remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT). Donor hematopoietic progenitor cells reconstitute the recipient\u2019s immune system after transplant, and newly generated donor-derived immune cells actively participate in propagating alloimmunity. Retinoic acid (RA) has well-known effects on the differentiation and proliferation of myeloid progenitor cells. We hypothesized that RA influences the reconstitution of some donor-derived myeloid cell populations after allogeneic HSCT. In a C57BL\/6 into Balb\/c murine allogeneic bone marrow transplantation (BMT) model, we found that Gr1\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    CD84\n                    <jats:sup>+<\/jats:sup>\n                    F4-80\n                    <jats:sup>-<\/jats:sup>\n                    myeloid-derived suppressor cells (MDSCs) accumulated in the spleen of recipient mice early after BMT. Notably, the absolute number of MDSCs was significantly reduced in RA-treated mice compared with DMSO-treated mice. Furthermore, MDSCs isolated from RA-treated recipient mice showed decreased immunosuppressive function in mixed lymphocyte reactions (MLRs). Bulk RNA-sequencing (RNA-seq) revealed that RA treatment alters transcriptional programs involving Wnt signaling and the CCL2-CCR2 axis in MDSCs. We found that adding RA to the MDSC culture promotes the differentiation of Ly6C\n                    <jats:sup>-<\/jats:sup>\n                    Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    granulocytic MDSCs. Thus, enhancing RA signaling causes both quantitative and qualitative changes of MDSCs after allogeneic HSCT. Recent studies have demonstrated an important role of donor intestinal CD103\n                    <jats:sup>+<\/jats:sup>\n                    dendrite cells (DCs) in propagating GVHD. We found that RA-treated recipient mice had significantly increased colonic CD103\n                    <jats:sup>+<\/jats:sup>\n                    DCs compared with DMSO-treated mice. On the contrary, vitamin A deficiency was associated with a significant reduction in the percentage and absolute number of CD103\n                    <jats:sup>+<\/jats:sup>\n                    DCs. To study the effects of RA on DCs\n                    <jats:italic>in vitro<\/jats:italic>\n                    , BM cells were cultured in the presence of GM-CSF. There was a significant increase in the percentage of CD11c\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    mucosal DCs in cultures exposed to RA. Furthermore, RA-exposed DCs exhibited increased MHC-II expression and enhanced T-cell stimulatory capacity. In summary, our study demonstrated that RA participates in regulating donor MDSC and colonic CD103\n                    <jats:sup>+<\/jats:sup>\n                    DC reconstitution after allogeneic HSCT. Therapeutic modulation of RA signaling or its downstream pathways may represent a strategy to limit alloimmunity and improve transplant outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1599346","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:32:15Z","timestamp":1790087535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Retinoic acid regulates donor myeloid-derived suppressor cell and colonic dendrite cell reconstitution after allogeneic hematopoietic stem cell transplantation in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinlei","family":"Li","sequence":"first","affiliation":[{"name":"Division of Hematology & Oncology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]},{"name":"Department of Medicine, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]},{"name":"Department of Medicine, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]},{"name":"Department of Medicine, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Limpert","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]},{"name":"Department of Medicine, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]},{"name":"Department of Medicine, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Zhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William 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