{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:03:03Z","timestamp":1790971383468,"version":"4.1.0"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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:p>The fibroblast growth factor (FGF)\/FGF receptor (FGFR) signaling system regulates tissue repair, angiogenesis, extracellular matrix remodeling, fibrosis, and bone metabolism. Although FGF\/FGFR biology has been extensively studied in oncology, development, and fibrotic lung disease, its relevance to systemic autoimmune rheumatic diseases remains scattered across disease-specific and unevenly supported literatures. This narrative, evidence-informed review synthesizes current evidence on FGF\/FGFR signaling in rheumatoid arthritis (RA), systemic lupus erythematosus\/lupus nephritis (SLE\/LN), systemic sclerosis (SSc), spondyloarthritis\/psoriatic arthritis (SpA\/PsA), and Sj\u00f6gren\u2019s disease. We explicitly distinguish mechanistically supported axes from biomarker-level associations and extrapolated regenerative concepts. In RA, FGF10\/FGFR1 and FGF2\/FGFR3 have the strongest tissue-level support, linking relapse-prone synovial fibroblast niches, fibroblast-like synoviocyte activation, angiogenesis, and bone erosion. In SLE\/LN, FGF23\/Klotho is best interpreted as an emerging renal-metabolic and inflammatory biomarker axis rather than a validated therapeutic target, although reported associations with urinary MCP-1\/CCL2 suggest testable links to renal chemokine-mediated inflammation. In SSc-ILD, nintedanib demonstrates that FGFR-containing multi-kinase networks are clinically tractable, but the FGFR-specific contribution remains unresolved. In SpA\/PsA, FGF2-mediated angiogenesis-osteogenesis coupling and FGF7\/FGFR2IIIb signaling provide candidate mechanisms for entheseal remodeling, whereas direct human entheseal validation is still lacking. In Sj\u00f6gren\u2019s disease, FGF7\/FGF10\/FGFR2b signaling supports a regenerative hypothesis derived mainly from salivary gland developmental biology and organoid studies. We propose an axis-prioritization translational framework that specifies ligand-receptor pairs, patient subgroups, validation tissues, delivery strategies, pharmacodynamic endpoints, and clinical or imaging readouts. This review is not a systematic review or meta-analysis; rather, it provides a structured roadmap for tissue-level validation, longitudinal biomarker studies, and short-course proof-of-mechanism trials before clinical translation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1875220","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:55:53Z","timestamp":1784699753000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["FGF\/FGFR signaling at the immune-stromal interface in autoimmune rheumatic diseases: from tissue remodeling to translational opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Sheng","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Rheumatology, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianbo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.006","article-title":"Immunopathogenesis of rheumatoid arthritis","volume":"46","author":"Firestein","year":"2017","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7","article-title":"Distinct fibroblast subsets drive inflammation and damage in arthritis","volume":"570","author":"Croft","year":"2019","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2025.06.008","article-title":"Cellular interactions in maintaining an inflammatory microenvironment in rheumatoid arthritis","volume":"184","author":"Ganeshalingam","year":"2025","journal-title":"Mol Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/med.21288","article-title":"FGF receptors: cancer biology and therapeutics","volume":"34","author":"Katoh","year":"2014","journal-title":"Med Res Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkac005","article-title":"Roles of the fibroblast growth factor signal transduction system in tissue injury repair","volume":"10","author":"Chen","year":"2022","journal-title":"Burns Trauma"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines14020396","article-title":"Fibroblast-like synoviocytes as key regulators of homeostasis and inflammation in the joint microenvironment of inflammatory arthritis","volume":"14","author":"Lee","year":"2026","journal-title":"Biomedicines"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0115-y","article-title":"Fibroblast growth factor receptors as treatment targets in clinical oncology","volume":"16","author":"Katoh","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00418","article-title":"Fgf10 signaling in lung development, homeostasis, disease, and repair after injury","volume":"9","author":"Yuan","year":"2018","journal-title":"Front Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/art.42674","article-title":"Role and therapeutic potential for targeting fibroblast growth factor 10\/FGFR1 in relapsed rheumatoid arthritis","volume":"76","author":"Meng","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903076","article-title":"Nintedanib for systemic sclerosis-associated interstitial lung disease","volume":"380","author":"Distler","year":"2019","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.55.5507","article-title":"Serum fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis","volume":"55","author":"Sato","year":"2016","journal-title":"Intern Med"},{"key":"B12","article-title":"FGF23-Klotho axis in patients with rheumatoid arthritis","volume":"38","author":"Alvarez-Cienfuegos","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7120558","article-title":"Fibroblast growth factor 23 to alpha-Klotho index correlates with systemic sclerosis activity: a proposal for novel disease activity marker","volume":"7","author":"Kotyla","year":"2018","journal-title":"J Clin Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.02.001","article-title":"Current status and future perspectives of FGF21 analogues in clinical trials","volume":"35","author":"Chui","year":"2024","journal-title":"Trends Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.176","article-title":"The fibroblast growth factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115778","article-title":"Fibroblast growth factor 2 in the hotbed of rheumatoid arthritis pathogenesis","volume":"168","author":"Illanad","year":"2026","journal-title":"Int Immunopharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2024.100801","article-title":"Primer on fibroblast growth factor 7 (FGF 7)","volume":"139","author":"Zheng","year":"2024","journal-title":"Differentiation"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2023.100741","article-title":"Fibroblast growth factor 10","volume":"139","author":"Rochais","year":"2024","journal-title":"Differentiation"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2792","article-title":"The FGF family: biology, pathophysiology and therapy","volume":"8","author":"Beenken","year":"2009","journal-title":"Nat Rev Drug Discov"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25094875","article-title":"Non-classical effects of FGF23: molecular and clinical features","volume":"25","author":"Mart\u00ednez-Heredia","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0386-0","article-title":"The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic","volume":"16","author":"Geng","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601252200","article-title":"Receptor specificity of the fibroblast growth factor family","volume":"281","author":"Zhang","year":"2006","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41419-018-0433-0","article-title":"Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis","volume":"9","author":"Lee","year":"2018","journal-title":"Cell Death Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24180","article-title":"FGF23 facilitates IL-1\u03b2 synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-\u03baB pathways","volume":"39","author":"Hu","year":"2024","journal-title":"Environ Toxicol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2780","article-title":"Fibroblast growth factor signalling: from development to cancer","volume":"10","author":"Turner","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ncb867","article-title":"Sprouty1 and Sprouty2 provide a control mechanism for the Ras\/MAPK signalling pathway","volume":"4","author":"Hanafusa","year":"2002","journal-title":"Nat Cell Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02701","article-title":"Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development","volume":"134","author":"Li","year":"2007","journal-title":"Development"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.01.004","article-title":"Fibroblast growth factor\/fibroblast growth factor receptor system in angiogenesis","volume":"16","author":"Presta","year":"2005","journal-title":"Cytokine Growth Factor Rev"},{"key":"B29","doi-asserted-by":"publisher","first-page":"14003","DOI":"10.1038\/boneres.2014.3","article-title":"Role of FGF\/FGFR signaling in skeletal development and homeostasis: learning from mouse models","volume":"2","author":"Su","year":"2014","journal-title":"Bone Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cytogfr.2017.04.003","article-title":"Fibroblast growth factor 2 as an antifibrotic: antagonism of myofibroblast differentiation and suppression of pro-fibrotic gene expression","volume":"35","author":"Dolivo","year":"2017","journal-title":"Cytokine Growth Factor Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-015-0251-9","article-title":"Treatment of CIA mice with FGF21 down-regulates TH17-IL-17 axis","volume":"39","author":"Li","year":"2016","journal-title":"Inflammation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.intimp.2015.01.005","article-title":"Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway","volume":"25","author":"Yu","year":"2015","journal-title":"Int Immunopharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210823","article-title":"Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis","volume":"76","author":"Huang","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13075-024-03308-7","article-title":"Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease","volume":"26","author":"Soldano","year":"2024","journal-title":"Arthritis Res Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01676-X","article-title":"FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition","volume":"22","author":"Cross","year":"2001","journal-title":"Trends Pharmacol Sci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1093\/rheumatology\/kew393","article-title":"Targeting non-canonical nuclear factor-\u03baB signalling attenuates neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis","volume":"56","author":"Maracle","year":"2017","journal-title":"Rheumatol (Oxford)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102791","article-title":"ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes","volume":"24","author":"Ma","year":"2021","journal-title":"iScience"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202631119","article-title":"FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis","volume":"119","author":"Zhu","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00689.x","article-title":"Melatonin inhibits human fibroblast-like synoviocyte proliferation via extracellular signal-regulated protein kinase\/P21(CIP1)\/P27(KIP1) pathways","volume":"47","author":"Nah","year":"2009","journal-title":"J Pineal Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217230","article-title":"Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)","volume":"80","author":"Spagnolo","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110628","article-title":"Pentraxin 3 inhibits fibroblast growth factor 2 induced osteoclastogenesis in rheumatoid arthritis","volume":"131","author":"Zhao","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1494-y","article-title":"The role of periostin in tissue remodeling across health and disease","volume":"71","author":"Conway","year":"2014","journal-title":"Cell Mol Life Sci"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.04.007","article-title":"Periostin, a multifunctional matricellular protein in inflammatory and tumor microenvironments","volume":"37","author":"Liu","year":"2014","journal-title":"Matrix Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.593269","article-title":"Connective tissue growth factor: from molecular understandings to drug discovery","volume":"8","author":"Chen","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.10.038","article-title":"CCN2\/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling","volume":"586","author":"Aoyama","year":"2012","journal-title":"FEBS Lett"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.577015","article-title":"Tenascin-C in osteoarthritis and rheumatoid arthritis","volume":"11","author":"Hasegawa","year":"2020","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1987","article-title":"Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease","volume":"15","author":"Midwood","year":"2009","journal-title":"Nat Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0068-0","article-title":"The role of osteopontin in inflammatory processes","volume":"3","author":"Lund","year":"2009","journal-title":"J Cell Commun Signal"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/biology14040428","article-title":"Osteopontin in chronic inflammatory diseases: mechanisms, biomarker potential, and therapeutic strategies","volume":"14","author":"Lang","year":"2025","journal-title":"Biol (Basel)"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/art.20668","article-title":"Rheumatoid synovial endothelial cells produce basic fibroblast growth factor and synergize with metalloproteinases","volume":"50","author":"Nakano","year":"2004","journal-title":"Arthritis Rheum"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1612950","article-title":"Targeting fibroblasts in pathological bone formation: mechanisms and treatments","volume":"13","author":"Zhang","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202403073","article-title":"FGF7 as an essential mediator for the onset of ankylosing enthesitis related to psoriatic dermatitis","volume":"8","author":"Ebihara","year":"2025","journal-title":"Life Sci Alliance"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.14735","article-title":"Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: The FORWARD randomized clinical trial","volume":"322","author":"Hochberg","year":"2019","journal-title":"JAMA"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-019-04298-5","article-title":"Evaluation of serum fibroblast growth factor-23 in patients with axial spondyloarthritis and its association with sclerostin, inflammation, and spinal damage","volume":"39","author":"Gercik","year":"2019","journal-title":"Rheumatol Int"},{"key":"B55","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/s41584-023-01040-1","article-title":"FGF signalling implicated in relapsing RA","volume":"19","author":"McHugh","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead220","article-title":"Fibroblast growth factor receptor 1 as a potential marker of terminal effector peripheral T helper cells in rheumatoid arthritis patients","volume":"62","author":"Etori","year":"2023","journal-title":"Rheumatol (Oxford)"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429261684231002062505","article-title":"Targeting FGFR3 is a useful therapeutic strategy for rheumatoid arthritis treatment","volume":"17","author":"Yu","year":"2024","journal-title":"Curr Mol Pharmacol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/ar2515","article-title":"Vascular involvement in rheumatic diseases: \u2018vascular rheumatology\u2019","volume":"10","author":"Szekanecz","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106529","article-title":"Identification of a novel extracellular inhibitor of FGF2\/FGFR signaling axis by combined virtual screening and NMR spectroscopy approach","volume":"134","author":"Pagano","year":"2023","journal-title":"Bioorg Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2026.117783","article-title":"CUL4A promotes glycolytic metabolism of fibroblast-like synoviocytes by targeting FGF2 in rheumatoid arthritis","volume":"247","author":"Sun","year":"2026","journal-title":"Biochem Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13018-021-02887-4","article-title":"miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt\/beta-catenin pathway","volume":"17","author":"Dong","year":"2022","journal-title":"J Orthop Surg Res"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00011-025-02012-9","article-title":"Roquin-1 interaction with Regnase-1 inhibits the progression of rheumatoid arthritis via suppressing FGF2 expression and NF-\u03baB pathway","volume":"74","author":"Wang","year":"2025","journal-title":"Inflammation Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188835","article-title":"A novel 3D spheroid model of rheumatoid arthritis synovial tissue incorporating fibroblasts, endothelial cells, and macrophages","volume":"14","author":"Philippon","year":"2023","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.molimm.2025.06.002","article-title":"Klotho promotes bone formation in rheumatoid arthritis-associated osteoporosis by modulating the Fgf23\/Fgfr1\/NF-\u03baB pathway and inhibiting ferroptosis","volume":"184","author":"Ji","year":"2025","journal-title":"Mol Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-019-09872-w","article-title":"Fibroblast growth factor-21 ameliorates rheumatoid arthritis by maintaining articular integrity","volume":"26","author":"Opoku","year":"2020","journal-title":"Int J Pept Res Ther"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.02.059","article-title":"FGF21 exerts comparable pharmacological efficacy with Adalimumab in ameliorating collagen-induced rheumatoid arthritis by regulating systematic inflammatory response","volume":"89","author":"Yu","year":"2017","journal-title":"BioMed Pharmacother"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01327-5","article-title":"FGF21 enhances therapeutic efficacy and reduces side effects of dexamethasone in treatment of rheumatoid arthritis","volume":"44","author":"Sun","year":"2021","journal-title":"Inflammation"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.12.022","article-title":"Serum levels of fibroblast growth factor 23 are elevated in patients with active lupus nephritis","volume":"91","author":"Resende","year":"2017","journal-title":"Cytokine"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3390\/biom13081222","article-title":"Relationship of fibroblast growth factor 23 serum levels with disease characteristics in systemic lupus erythematosus patients","volume":"13","author":"Fern\u00e1ndez-Cladera","year":"2023","journal-title":"Biomolecules"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.2147\/ijnrd.s326399","article-title":"Accelerated atherosclerosis in systemic lupus erythematosus: Role of fibroblast growth factor 23- phosphate axis","volume":"14","author":"Ammar","year":"2021","journal-title":"Int J Nephrol Renovasc Dis"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.110201","article-title":"Monocyte chemoattractant-1 as a urinary biomarker for the diagnosis of activity of lupus nephritis in Brazilian patients","volume":"39","author":"Rosa","year":"2012","journal-title":"J Rheumatol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2020.100042","article-title":"Urinary biomarkers in lupus nephritis","volume":"3","author":"Aragon","year":"2020","journal-title":"J Transl Autoimmun"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0263778","article-title":"Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios","volume":"17","author":"Ngamjanyaporn","year":"2022","journal-title":"PloS One"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/salqon","article-title":"Alpha-Klotho protein in systemic lupus erythematosus","volume":"41","author":"Mart\u00edn-Gonz\u00e1lez","year":"2023","journal-title":"Clin Exp Rheumatol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.clim.2016.03.001","article-title":"Soluble \u03b1-klotho is a potential biomarker associated with neuropsychiatric systemic lupus erythematosus","volume":"165","author":"Ushigusa","year":"2016","journal-title":"Clin Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.177229","article-title":"Klotho supplementation decreases blood pressure and albuminuria in mice with lupus nephritis","volume":"988","author":"Takenaka","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111875","article-title":"Fibroblast growth factor 21 mitigates lupus nephritis progression via the FGF21\/Irgm 1\/NLRP3 inflammasome pathway","volume":"131","author":"Zou","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.10.003","article-title":"microRNA-199a may be involved in the pathogenesis of lupus nephritis via modulating the activation of NF-\u03baB by targeting Klotho","volume":"103","author":"Ye","year":"2018","journal-title":"Mol Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2020.10.021","article-title":"Association between the anti-aging gene Klotho and selected rheumatologic autoimmune diseases","volume":"361","author":"Russell","year":"2021","journal-title":"Am J Med Sci"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000043788","article-title":"Association between Klotho and autoimmune diseases: A Mendelian randomization study and cross-sectional study","volume":"104","author":"Ye","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"17300","DOI":"10.1038\/s41598-020-74179-6","article-title":"Dermal fibroblasts have different extracellular matrix profiles induced by TGF-\u03b2, PDGF and IL-6 in a model for skin fibrosis","volume":"10","author":"Juhl","year":"2020","journal-title":"Sci Rep"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04470-8","article-title":"The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease","volume":"16","author":"Wang","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020517","article-title":"An FGF2-derived short peptide attenuates bleomycin-induced pulmonary fibrosis by inhibiting collagen deposition and epithelial-mesenchymal transition via the FGFR\/MAPK signaling pathway","volume":"26","author":"Wang","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131784","article-title":"Single-cell analysis of ADSC interactions with fibroblasts and endothelial cells in scleroderma skin","volume":"12","author":"Frommer","year":"2023","journal-title":"Cells"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/168724","article-title":"Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha","volume":"33","author":"Kosa\u0142ka-W\u0119giel","year":"2024","journal-title":"Adv Clin Exp Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1900161","DOI":"10.1183\/13993003.00161-2019","article-title":"Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases","volume":"54","author":"Wollin","year":"2019","journal-title":"Eur Respir J"},{"key":"B87","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1124\/jpet.117.244129","article-title":"Triple angiokinase inhibitor nintedanib directly inhibits tumor cell growth and induces tumor shrinkage via blocking oncogenic receptor tyrosine kinases","volume":"364","author":"Hilberg","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207109","article-title":"Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis","volume":"75","author":"Huang","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B89","article-title":"Antifibrotic efficacy of nintedanib in a cellular model of systemic sclerosis-associated interstitial lung disease","author":"Atanelishvili","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217331","article-title":"Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial","volume":"79","author":"Seibold","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01286-x","article-title":"Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects","volume":"31","author":"Di Battista","year":"2023","journal-title":"Inflammopharmacology"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/s2665-9913(22)00215-6","article-title":"Safety and tolerability of nintedanib in patients with interstitial lung diseases in subgroups by sex: a post-hoc analysis of pooled data from four randomised controlled trials","volume":"4","author":"Hoffmann-Vold","year":"2022","journal-title":"Lancet Rheumatol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2025.152891","article-title":"Benefits of nintedanib continuation in systemic autoimmune rheumatic disease-related progressive pulmonary fibrosis: KEIO-SARD-ILD-cohort","volume":"76","author":"Suzuki","year":"2026","journal-title":"Semin Arthritis Rheum"},{"key":"B94","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/RHU.0000000000002281","article-title":"Real-world outcomes and tolerability of nintedanib in patients with systemic autoimmune rheumatic disease-associated interstitial lung disease: A retrospective study from a single center in a Middle Eastern population","volume":"32","author":"Namas","year":"2026","journal-title":"J Clin Rheumatol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002859","article-title":"Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression","volume":"9","author":"Khanna","year":"2023","journal-title":"RMD Open"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-023-06623-7","article-title":"Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: data from the INBUILD trial","volume":"42","author":"Matteson","year":"2023","journal-title":"Clin Rheumatol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1002\/art.42075","article-title":"Nintedanib in patients with autoimmune disease-related progressive fibrosing interstitial lung diseases: Subgroup analysis of the INBUILD trial","volume":"74","author":"Matteson","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2012.08.003","article-title":"Pathophysiology of new bone formation and ankylosis in spondyloarthritis","volume":"38","author":"Lories","year":"2012","journal-title":"Rheum Dis Clin North Am"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202310_34160","article-title":"The relationship between Salusin-\u03b1, Salusin-\u03b2, and Klotho levels with subclinical atherosclerosis in ankylosing spondylitis","volume":"27","author":"Tocoglu","year":"2023","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3390\/jcm15010131","article-title":"Assessment of cardiovascular risk and examination of blood Klotho levels in patients with ankylosing spondylitis","volume":"15","author":"Dogan","year":"2026","journal-title":"J Clin Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3332","article-title":"SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis","volume":"39","author":"Ma","year":"2021","journal-title":"Stem Cells"},{"key":"B102","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/s13075-019-2088-3","article-title":"Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis","volume":"21","author":"Fromm","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.16588","article-title":"Serum levels of angiogenesis-related factors in patients with psoriasis","volume":"50","author":"Watanabe","year":"2023","journal-title":"J Dermatol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2014.10.008","article-title":"Bone formation in axial spondyloarthritis","volume":"28","author":"Lories","year":"2014","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.70276","article-title":"Serum levels of 54 cytokines and chemokines reveal distinct inflammatory signatures in ankylosing spondylitis","volume":"13","author":"Li","year":"2025","journal-title":"Immun Inflammation Dis"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1242\/dev.146019","article-title":"Fgf10 and Sox9 are essential for the establishment of distal progenitor cells during mouse salivary gland development","volume":"144","author":"Chatzeli","year":"2017","journal-title":"Development"},{"key":"B107","doi-asserted-by":"publisher","first-page":"6485","DOI":"10.1038\/s41467-023-42243-0","article-title":"FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation","volume":"14","author":"Aure","year":"2023","journal-title":"Nat Commun"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110663","article-title":"A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands","volume":"39","author":"Mauduit","year":"2022","journal-title":"Cell Rep"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.1.21","article-title":"Role of FGF10\/FGFR2b signaling in homeostasis and regeneration of adult lacrimal gland and corneal epithelium proliferation","volume":"64","author":"Finburgh","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200167","article-title":"Single-cell RNA sequencing reveals PDGFR\u03b1+ stromal cell subpopulations that promote proacinar cell differentiation in embryonic salivary gland organoids","volume":"149","author":"Moskwa","year":"2022","journal-title":"Development"},{"key":"B111","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1186\/s13287-022-03033-5","article-title":"Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes","volume":"13","author":"Zhang","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.208728","article-title":"FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland organoids","volume":"131","author":"Hosseini","year":"2018","journal-title":"J Cell Sci"},{"key":"B113","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.biomaterials.2018.06.011","article-title":"Engineering innervated secretory epithelial organoids by magnetic three-dimensional bioprinting for stimulating epithelial growth in salivary glands","volume":"180","author":"Adine","year":"2018","journal-title":"Biomaterials"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.04.049","article-title":"Synergistic effects of laminin-1 peptides, VEGF and FGF9 on salivary gland regeneration","volume":"91","author":"Nam","year":"2019","journal-title":"Acta Biomater"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817323","article-title":"Erdafitinib in locally advanced or metastatic urothelial carcinoma","volume":"381","author":"Loriot","year":"2019","journal-title":"N Engl J Med"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1200\/PO-24-00896","article-title":"Safety and activity of fibroblast growth factor receptor inhibitors in advanced Malignancies: A pooled analysis of early-phase clinical trials","volume":"9","author":"Grochot","year":"2025","journal-title":"JCO Precis Oncol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01330-y","article-title":"Pemigatinib: first approval","volume":"80","author":"Hoy","year":"2020","journal-title":"Drugs"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3475","article-title":"A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of burosumab, an anti-FGF23 antibody, in adults with X-linked hypophosphatemia: Week 24 primary analysis","volume":"33","author":"Insogna","year":"2018","journal-title":"J Bone Miner Res"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)31785-9","article-title":"Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial","volume":"392","author":"Sanyal","year":"2018","journal-title":"Lancet"},{"key":"B120","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1056\/NEJMoa2304286","article-title":"Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH","volume":"389","author":"Loomba","year":"2023","journal-title":"N Engl J Med"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(25)00067-6","article-title":"Efimosfermin alfa (BOS-580), a long-acting FGF21 analogue, in participants with phenotypic metabolic dysfunction-associated steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial","volume":"10","author":"Loomba","year":"2025","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B122","article-title":"A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis","volume":"34","author":"Dahlberg","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216453","article-title":"Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial","volume":"79","author":"Eckstein","year":"2020","journal-title":"Ann Rheum Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1875220\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:55:55Z","timestamp":1784699755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1875220\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":123,"alternative-id":["10.3389\/fimmu.2026.1875220"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1875220","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1875220"}}