{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:54:49Z","timestamp":1776315289280,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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":"\n Background<\/jats:title>\n \n Ankylosing spondylitis (AS) is a chronic inflammatory disorder predominantly affecting the sacroiliac and spinal joints. Emerging evidence indicates that N\n 6<\/jats:sup>\n -methyladenosine (m\n 6<\/jats:sup>\n A) RNA modification plays a critical role in inflammatory regulation. Xinfeng Capsule (XFC), a Traditional Chinese Medicine formula (Xin\u2019an medicine), has demonstrated clinical efficacy in alleviating AS-associated inflammation. However, whether XFC modulates AS pathology through m\n 6<\/jats:sup>\n A-dependent epigenetic mechanisms remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n This study aimed to investigate whether XFC mitigates AS inflammation by regulating the IL-17\/NF-\u03baB pathway via m\n 6<\/jats:sup>\n A modification.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Core therapeutic targets were identified by integrating network pharmacology with RNA-sequencing data. The direct interaction between YTHDC1 and LINC01579 was validated using RNA pull-down and dual-luciferase reporter assays. To identify the functional m6A sites, site-directed mutagenesis of two putative m6A motifs (MUT1 and MUT2) in LINC01579 was performed, and the effects of YTHDC1 knockdown were assessed. An\n in vitro<\/jats:italic>\n co-culture model comprising AS patient-derived fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMC) was established, alongside an\n in vivo<\/jats:italic>\n proteoglycan-induced arthritis (PGIA) mouse model. To verify the underlying mechanism, gain- and loss-of-function experiments were conducted using overexpression plasmids and small interfering RNAs (siRNAs) targeting LINC01579 and YTHDC1. m\n 6<\/jats:sup>\n A levels were quantified by MeRIP-qPCR. Inflammation and pathway activation were assessed via immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA). RNA stability was evaluated using actinomycin D assays, while cell migration was measured by scratch assays. Bone destruction was analyzed using micro-CT and histological staining. Additionally, an IL-17 pathway inhibitor (AIN457) and agonist (SR0987) were employed to validate pathway involvement.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Bioinformatics and network pharmacology analysis identified LINC01579 as a core gene in AS inflammation and YTHDC1 as an upstream regulator of LINC01579 m\n 6<\/jats:sup>\n A modification. RNA pull-down assays confirmed the direct binding of YTHDC1 to LINC01579.Functional studies revealed that mutation of the MUT1 site abolished the regulatory effects of YTHDC1 knockdown on inflammatory cytokines (IL-17, IL-6, TNF-\u03b1) and LINC01579 expression. XFC was predicted to inhibit inflammation via the IL-17\/NF-\u03baB pathway.\n In vitro<\/jats:italic>\n , LINC01579 knockdown significantly enhanced the release of inflammatory mediators and activated IL-17\/NF-\u03baB signaling. Conversely, YTHDC1 overexpression increased LINC01579 m\n 6<\/jats:sup>\n A levels, leading to its downregulation. XFC treatment effectively reduced YTHDC1 expression and LINC01579 m\n 6<\/jats:sup>\n A modification, thereby restoring LINC01579 levels and suppressing IL-17\/NF-\u03baB activation.\n In vivo<\/jats:italic>\n , XFC ameliorated joint inflammation, bone erosion, and joint space narrowing in PGIA mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n XFC alleviates AS progression by inhibiting YTHDC1-mediated m6A modification of LINC01579, which prevents its degradation and subsequently dampens IL-17\/NF-\u03baB pathway activation. These findings highlight a potential epigenetic mechanism underlying the therapeutic effects of XFC in AS.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762062","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:21:17Z","timestamp":1776313277000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Xinfeng capsule attenuates ankylosing spondylitis by downregulating YTHDC1-mediated m6A modification of LINC01579 and suppressing IL-17\/NF-\u03baB signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiang","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Institute of Rheumatology, Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Institute of Rheumatology, Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"First Clinical Medical College, Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian-Heng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"First Clinical Medical College, Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Institute of Rheumatology, Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01250-5","article-title":"Genotype by sex interactions in ankylosing spondylitis","volume":"55","author":"Li","year":"2023","journal-title":"Nat Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.21037\/qims-24-729","article-title":"Artificial intelligence improves the diagnosis of human leukocyte antigen (HLA)-B27-negative axial spondyloarthritis based on multi-sequence magnetic resonance imaging and clinical features","volume":"14","author":"Lu","year":"2024","journal-title":"Quant. 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