{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:47:29Z","timestamp":1785822449385,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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>Introduction<\/jats:title>\n                    <jats:p>Macrophage-driven inflammatory programs and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role for periodontal tissue destruction; however, the transcriptional regulators that mediate these responses remain unclear. This study therefore examined the role of the microRNA-1260b (miR-1260b)\u2013nuclear factor of activated T-cells 5 (NFAT5) axis in inflammatory macrophage responses relevant to periodontal disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NFAT5 was identified as a candidate miR-1260b target using integrated bioinformatic screening and investigated through gain- and loss-of-function approaches in RAW264.7 macrophages. Inflammasome-related experiments were performed in J774A.1 macrophages using an LPS\/ATP two-signal stimulation protocol. Further analyses included a ligature-induced mouse experimental periodontitis model with local NFAT5 small interfering RNA delivery, macrophage polarization assays in murine bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-\u03b3), and validation experiments in human peripheral blood mononuclear cell (PBMC)\u2013derived macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transfection with miR-1260b reduced NFAT5 expression and attenuated LPS-induced nuclear accumulation in macrophages.\n                      <jats:italic>In vivo<\/jats:italic>\n                      analyses showed increased NFAT5 expression in inflamed gingival tissues, whereas local NFAT5 knockdown was associated with reduced NLRP3 and interleukin-1 beta (IL-1\u03b2) expression. In J774A.1 macrophages, NFAT5 silencing under LPS\/ATP stimulation reduced Nlrp3 and Il1b mRNA expression, together with lower NLRP3 and pro-IL-1\u03b2 protein levels and reduced IL-1\u03b2 levels in culture supernatants. Additional\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments demonstrated reduced M1-associated inflammatory gene expression following NFAT5 silencing. Flow cytometric analysis further showed a reduced proportion of CD86\n                      <jats:sup>+<\/jats:sup>\n                      macrophage subsets after NFAT5 knockdown, accompanied by decreased pro-inflammatory cytokine production in both murine and human macrophage systems.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify NFAT5 as a key regulator of inflammasome priming that contributes to inflammatory macrophage polarization in periodontal inflammation and suggest the miR-1260b\u2013NFAT5 axis as a potential target for host-modulatory approaches.<\/jats:p>\n                  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