{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:54:00Z","timestamp":1787792040963,"version":"build-2784847793"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01- DE030415"],"award-info":[{"award-number":["R01- DE030415"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tissue-resident fibroblasts are heterogeneous and provide an endogenous source of cytokines that regulate immunologic events in many osteolytic diseases. Identifying distinct inflammatory fibroblast subsets and conducting mechanistic\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies are critical for understanding disease pathogenesis and precision therapeutics, which is poorly explored in periodontitis. Here, we surveyed published single-cell datasets for fibroblast-specific analysis and show that Intercellular Adhesion Molecule-1 (ICAM1) expression selectively defines a fibroblast subset that exhibits an inflammatory transcriptional profile associated with nuclear factor-\u03baB (NF-\u03baB) pathway. ICAM1\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts expand in both human periodontitis and murine ligature-induced periodontitis model, which have upregulated expression of CCL2 and CXCL1 compared to other fibroblast populations. Using a mouse model to selectively target gingival stromal cells, we further show that disruption of an inflammatory pathway by inhibiting transcriptional activity of NF-\u03baB in these cells accelerated periodontal bone loss. Mechanistically, this was linked to a reduction of CCL2 expression by the ICAM1\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts, leading to impaired macrophage recruitment and efferocytosis that was associated with persistent neutrophilic inflammation. These results may have a significant therapeutic implication as ICAM1\n                    <jats:sup>+<\/jats:sup>\n                    gingival fibroblasts exert a protective response by regulating innate immune responses that are needed for the controlled inflammatory events in early stages of periodontitis.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1484483","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:12:55Z","timestamp":1732234375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["ICAM1+ gingival fibroblasts modulate periodontal inflammation to mitigate bone loss"],"prefix":"10.3389","volume":"15","author":[{"given":"William 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