{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:57:37Z","timestamp":1790585857758,"version":"4.1.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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>\n                      Polyostotic fibrous dysplasia (POFD) is a mosaic skeletal disorder driven by somatic\n                      <jats:italic>GNAS<\/jats:italic>\n                      mutations that constitutively activate Gs\u03b1-cAMP signaling, producing fibro-osseous craniofacial deformities. POFD lesions are histologically classified into three subtypes\u2014Type I (connective-tissue predominant), Type II (cancellous-bone predominant), and Type III (sclerotic-bone predominant)\u2014yet the immune microenvironment across these categories remains undefined. This study aims to dissect lymphoid and myeloid heterogeneity and inter-cellular communication networks among distinct POFD histological categories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single-cell RNA sequencing on maxillary lesion tissues from three age- and sex-matched POFD patients classified as Type I (n=1), Type II (n=1), and Type III (n=1). After stringent quality control, 24,567 cells (median 1,762 genes\/cell) were integrated and clustered. Ligand\u2013receptor interactions were inferred using CellChat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four major lineages were resolved: mesenchyme, lymphoid, myeloid, endovascular. Lymphoid representation differed across subtypes (Type I 1.00%, Type II 5.10%, Type III 10.90%), whereas endovascular fractions showed an inverse pattern (Type I 25.10%, Type II 9.90%, Type III 4.50%). Sub-clustering identified five lymphoid and six myeloid subsets. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were most abundant in Type I (51.10%) but less represented in Type II (36.50%) and Type III (29.30%). CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells constituted 2.10%, 11.90%, and 11.20% across Types I-III, respectively; germinal-center (GC) B cells were undetectable in Type I, minor in Type II (~1.60%), and prominent in Type III (~29.20%). Among myeloid cells, M1 macrophages comprised 9.90% in Type I, 25.70% in Type II, and 15.30% in Type III; osteoclasts were abundant in Type I (35.40%) but scarce in Types II and III (&amp;lt;5%). Dendritic cells (DCs) were absent in Type I yet detectable in Type II (1.90%) and Type III (2.60%). Network-central genes included\n                      <jats:italic>LTB<\/jats:italic>\n                      ,\n                      <jats:italic>TXNIP<\/jats:italic>\n                      ,\n                      <jats:italic>FTH1<\/jats:italic>\n                      , and\n                      <jats:italic>PABPC1<\/jats:italic>\n                      for CD4\n                      <jats:sup>+<\/jats:sup>\n                      and GC B cells, and\n                      <jats:italic>S100A8\/9<\/jats:italic>\n                      ,\n                      <jats:italic>CXCL8<\/jats:italic>\n                      ,\n                      <jats:italic>CCL2\/3\/4<\/jats:italic>\n                      , and\n                      <jats:italic>IL1B<\/jats:italic>\n                      for M1 macrophages and monocytes. Inter-cellular communication networks differed markedly by subtype: Type I and II displayed relatively simple interactomes, whereas Type III exhibited densely interconnected signaling with strengthened M2 macrophage-monocyte, M2 macrophage-GC B cell (CXCL12-CXCR4, APP-CD74), and GC B cell-monocyte axes, alongside attenuated CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell-GC B cell (CLEC2D-KLRB1, ADGRE5-CD55) and M1 macrophage-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell crosstalk. Pathway enrichment revealed subtype-specific activation of oxidative phosphorylation, NF-\u03baB, and antigen-presentation cascades across lymphoid and myeloid compartments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides the first single-cell immune atlas of POFD, delineating lymphoid and myeloid heterogeneity across three histological subtypes. The identified subtype-specific markers and inter-cellular communication architectures offer candidate biomarkers for diagnostic stratification and reveal potential immunomodulatory targets for this disfiguring bone disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906418","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:22:14Z","timestamp":1790583734000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell landscape of lymphoid and myeloid heterogeneity across type-stratified craniofacial lesions in polyostotic fibrous dysplasia"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui-Chuan","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai 9th People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, 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