{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:05:22Z","timestamp":1793203522176,"version":"4.5.0"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019832","name":"Galapagos NV","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100019832","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>Adaptive immune responses are widely considered the primary drivers of chronic inflammation in autoimmune disease, yet increasing evidence suggests that dysregulated myeloid cells play a central role in sustaining tissue damage. Salt-inducible kinases (SIKs) regulate immune cell activation, and their pharmacological inhibition can promote a shift from proinflammatory toward an immunoregulatory phenotype. We investigated whether selective inhibition of SIK2 and SIK3 with GLPG3970 could reprogram monocytes, macrophages, and dendritic cells, and we assessed pharmacological effects on activated T and B cells. Preclinical studies in mouse models of colitis, psoriasis, and arthritis demonstrated that SIK2\/SIK3 inhibition reduced inflammatory activity and promoted immunoregulatory and tolerogenic-associated pathways. Clinical signal-detection studies in ulcerative colitis, psoriasis, and rheumatoid arthritis revealed signs of clinical and biological activity in ulcerative colitis and psoriasis. These findings suggest that myeloid cell dysfunction and impaired myeloid phenotype switching contribute to chronic inflammation in autoimmune diseases and that therapeutic targeting of SIK2\/SIK3 holds the potential to restore immune balance by converting proinflammatory into regulatory pathways. Collectively, this work supports SIK2\/SIK3 inhibition as a potential treatment strategy for myeloid cell\u2013driven chronic inflammatory conditions.<\/jats:p>","DOI":"10.1172\/jci.insight.171776","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T19:00:48Z","timestamp":1770577248000},"source":"Crossref","is-referenced-by-count":4,"title":["Selective SIK2\/SIK3 inhibition reprograms pro- and antiinflammatory pathways in myeloid cells, improving autoimmune disease outcomes"],"prefix":"10.1172","volume":"11","author":[{"given":"Steve","family":"De Vos","sequence":"first","affiliation":[{"name":"Galapagos NV, Mechelen, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Desroy","sequence":"additional","affiliation":[{"name":"Galapagos SASU, Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Bellaire","sequence":"additional","affiliation":[{"name":"Galapagos 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