{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T04:05:15Z","timestamp":1783137915986,"version":"3.54.6"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/01\/COE\/07\/UDSC\/2008\u2010Phase\u2010I"],"award-info":[{"award-number":["BT\/01\/COE\/07\/UDSC\/2008\u2010Phase\u2010I"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/COE\/34\/SP15246\/2015\u2010Phase\u2010II"],"award-info":[{"award-number":["BT\/COE\/34\/SP15246\/2015\u2010Phase\u2010II"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n \n ARL15<\/jats:italic>\n , coding for a small GTPase, was identified as a non\u2010HLA susceptibility gene in rheumatoid arthritis (RA) through a GWAS in a North Indian cohort, with serum adiponectin and ARL15 levels higher in RA patients with the associated genotype. This study aimed to delineate the functional role of\n ARL15<\/jats:italic>\n in RA pathobiology.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Differential transcriptomics in both ex\u00a0vivo RA synovial fibroblasts and in\u00a0vitro MH7A cells using a gene knockdown (KD) approach and standard analyses pipeline were performed to obtain insights into\n ARL15<\/jats:italic>\n 's role.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In RASF,\n ARL15<\/jats:italic>\n KD led to downregulation of\n COMP\u2014an<\/jats:italic>\n extracellular matrix stabilizer linked to severe RA\u2014alongside upregulation of adiponectin and IFN response genes like\n IFI6<\/jats:italic>\n and\n USP18<\/jats:italic>\n . Furthermore, upregulation of\n NPTX1<\/jats:italic>\n and\n MX1<\/jats:italic>\n , previously associated with disease modulation and treatment response, was observed. Downregulation of\n CTGF<\/jats:italic>\n ,\n CD248<\/jats:italic>\n , and\n PTX3<\/jats:italic>\n suggested involvement of\n ARL15<\/jats:italic>\n in inflammation and RA\u2010associated cardiovascular risk. Conversely,\n ARL15<\/jats:italic>\n KD in MH7A cells displayed distinct signatures with upregulated cytokines (\n IL1A, IL8, CXCLs<\/jats:italic>\n ) and downregulated inflammatory regulators (\n DOCK2, TLR4, TGFB2<\/jats:italic>\n ), reflecting an inflammatory bias distinct from patient\u2010derived RASF.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The dual\u2010system approach, despite its divergent differential expression, underscores the multifaceted role of\n ARL15<\/jats:italic>\n in regulating connective tissue architecture, inflammation, and immune response. Limitations of immortalized cell models in capturing patient heterogeneity and disease complexity are apparent, but the key findings position\n ARL15<\/jats:italic>\n as a promising therapeutic target, warranting further investigation in RA animal models and genomic medicine. Taken together, this work provides a compelling rationale to pursue ARL\n 15<\/jats:italic>\n targeted interventions in RA management.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1756-185x.70668","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T06:18:41Z","timestamp":1778048321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dissecting\n \n ARL15<\/i>\n <\/scp>\n Function in Rheumatoid Arthritis: Insights From Ex\u00a0Vivo and in Vitro Synovial Fibroblast Models"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-1217","authenticated-orcid":false,"given":"Sujit","family":"Kashyap","sequence":"first","affiliation":[{"name":"Department of Genetics University of Delhi South Campus New Delhi India"},{"name":"Feinberg School of Medicine Northwestern University Chicago USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Delhi South Campus New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paritosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Delhi South Campus New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maumita","family":"Kanjilal","sequence":"additional","affiliation":[{"name":"Rheumatology Department All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Kumar","sequence":"additional","affiliation":[{"name":"Rheumatology Department All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-5443","authenticated-orcid":false,"given":"B. K.","family":"Thelma","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Delhi South Campus New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(03)00259-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00648.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.190"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh199"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151222279"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13041324"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2462"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12873"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213678"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38110"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-63790-6"},{"issue":"4","key":"e_1_2_9_14_1","first-page":"581","article-title":"Functional Characterisation of ADP Ribosylation Factor\u2010Like Protein 15 in Rheumatoid Arthritis Synovial Fibroblasts","volume":"36","author":"Kashyap S.","year":"2018","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11603"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2014.05.023"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X16643340"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17746-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"issue":"2","key":"e_1_2_9_20_1","first-page":"301","article-title":"Fibroblast\u2010Like Synovial Cells Derived From Synovial Fluid","volume":"32","author":"Stebulis J. 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