{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:06:58Z","timestamp":1792390018319,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705403"],"award-info":[{"award-number":["2023YFC2705403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC 92478122, NSFC 92357306, NSFC 32370914, NSFC 82371673, NSFC 92057119, NSFC 31970798"],"award-info":[{"award-number":["NSFC 92478122, NSFC 92357306, NSFC 32370914, NSFC 82371673, NSFC 92057119, NSFC 31970798"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1408200"],"award-info":[{"award-number":["23ZR1408200"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"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>Decidual macrophages maintain immune tolerance and support decidualization at the maternal\u2013fetal interface. However, the heterogeneity and functions of macrophage subsets in recurrent spontaneous abortion (RSA) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated single-cell RNA sequencing of human endometrium and decidua with clinical validation. Functional assays using THP-1\u2013derived macrophages and the co-culture with decidual stromal cells were performed to characterize macrophage subsets and investigate their roles in decidualization and RSA pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A subset of FOLR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages enriched in the decidua showed an M2-like immunoregulatory phenotype. In RSA decidua, FOLR2 expression and the proportion of FOLR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages were markedly reduced, accompanied by increased inflammatory signaling and impaired angiogenic and adhesion interactions. Functional assays showed that FOLR2 overexpression enhanced immunoregulatory, tissue-resident, and pro-angiogenic properties, whereas FOLR2 silencing promoted inflammatory responses and impaired angiogenesis. Reciprocal crosstalk between DSCs and FOLR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages established a positive feedback loop that promoted stromal decidualization and supported pregnancy maintenance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      FOLR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages represent an immunoregulatory subset at the maternal\u2013fetal interface with tissue-resident and pro-angiogenic features. The loss of FOLR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages in RSA may contribute to immune dysregulation and defective decidualization, providing new insights into the immune mechanisms underlying RSA pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1852410","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:34:35Z","timestamp":1782189275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune activation induced by FOLR2+ decidual macrophage deficiency impairs decidualization and angiogenesis in spontaneous abortion"],"prefix":"10.3389","volume":"17","author":[{"given":"Si-Man","family":"Chen","sequence":"first","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive 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