{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:41:14Z","timestamp":1774442474017,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic inflammatory condition of the colon with heterogeneous patient responses to treatment. Janus kinase (JAK) inhibitors such as filgotinib reduce inflammation through the blockade of cytokine signaling. We sought to characterize the mechanism of action of filgotinib on peripheral immune cells to improve our understanding of dysregulated cell populations in UC and their response to treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells (PBMCs) were isolated from UC patients at baseline or after 10\u2009weeks of filgotinib treatment in the SELECTION trial. PBMCs were analyzed alongside healthy controls by flow cytometry and sorted into 12 cell populations for transcriptome sequencing to correlate with treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following 10\u2009weeks of filgotinib treatment, changes in the frequency of peripheral B cell populations were observed, with more significant changes seen in treatment-responsive patients in memory B cells and plasmablasts. Transcriptomic changes associated with filgotinib treatment were modest but overall reverted UC-induced gene expression changes toward control samples in B cells and phagocytic mononuclear cells. These changes were greater in treatment-responsive than in non-responsive patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Filgotinib response was associated with normalization of the cellular frequency and gene expression levels of B cells and phagocytic mononuclear cells in UC patients, resulting in immune profiles resembling those of healthy controls.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag028","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:58:12Z","timestamp":1774432692000},"source":"Crossref","is-referenced-by-count":0,"title":["Filgotinib treatment modulates frequency and gene expression of circulating immune cell subsets in ulcerative colitis"],"prefix":"10.1093","volume":"20","author":[{"given":"Emily R","family":"Wendt","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Park","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan C","family":"Hindmarch","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramya","family":"Kongala","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M","family":"Shows","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angie","family":"Hertz","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladislav","family":"Malkov","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Billin","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8961-3660","authenticated-orcid":false,"given":"James D","family":"Lord","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"2026032505580851200_jjag028-B1","doi-asserted-by":"crossref","first-page":"7186","DOI":"10.3390\/jcm13237186","article-title":"Efficacy and safety of janus kinase-inhibitors in ulcerative colitis","volume":"13","author":"Neri","year":"2024","journal-title":"J Clin Med"},{"key":"2026032505580851200_jjag028-B2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/369333a0","article-title":"Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation","volume":"369","author":"Nelson","year":"1994","journal-title":"Nature"},{"key":"2026032505580851200_jjag028-B3","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The molecular details of cytokine signaling via the JAK\/STAT pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein Sci"},{"key":"2026032505580851200_jjag028-B4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.16.1.293","article-title":"Jaks and STATs: biological implications","volume":"16","author":"Leonard","year":"1998","journal-title":"Annu Rev Immunol"},{"key":"2026032505580851200_jjag028-B5","doi-asserted-by":"crossref","first-page":"2040620720914489","DOI":"10.1177\/2040620720914489","article-title":"Insights into the role of the JAK\/STAT signaling pathway in graft-versus-host disease","volume":"11","author":"Abboud","year":"2020","journal-title":"Ther Adv Hematol"},{"key":"2026032505580851200_jjag028-B6","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/ecco-jcc\/jjad173","article-title":"Janus kinase inhibitors differentially inhibit specific cytokine signals in the mesenteric lymph node cells of inflammatory bowel disease patients","volume":"18","author":"Hindmarch","year":"2024","journal-title":"J Crohns Colitis"},{"key":"2026032505580851200_jjag028-B7","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/annrheumdis-2020-219012","article-title":"JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib","volume":"80","author":"Traves","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"2026032505580851200_jjag028-B8","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/S0140-6736(21)00666-8","article-title":"Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b\/3 double-blind, randomised, placebo-controlled trial","volume":"397","author":"Feagan","year":"2021","journal-title":"Lancet"},{"key":"2026032505580851200_jjag028-B9","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1084\/jem.190.9.1241","article-title":"Human G protein-coupled receptor GPR-9-6\/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis","volume":"190","author":"Zabel","year":"1999","journal-title":"J Exp Med"},{"key":"2026032505580851200_jjag028-B10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41556-018-0223-z","article-title":"Integrin trafficking in cells and tissues","volume":"21","author":"Moreno-Layseca","year":"2019","journal-title":"Nat Cell Biol"},{"key":"2026032505580851200_jjag028-B11","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1084\/jem.20080397","article-title":"Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor","volume":"205","author":"Cosmi","year":"2008","journal-title":"J Exp Med"},{"key":"2026032505580851200_jjag028-B12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clim.2018.03.002","article-title":"Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers","volume":"191","author":"Weinhold","year":"2018","journal-title":"Clin Immunol"},{"key":"2026032505580851200_jjag028-B13","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/bjd.12517","article-title":"Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters during 12 weeks of psoriasis treatment","volume":"169","author":"Strober","year":"2013","journal-title":"Br J Dermatol"},{"key":"2026032505580851200_jjag028-B14","article-title":"Mediators of filgotinib treatment effects in ulcerative colitis: exploring circulating biomarkers in the phase 2b\/3 SELECTION study","author":"Nakase","year":"2024","journal-title":"Inflamm Bowel Dis"},{"key":"2026032505580851200_jjag028-B15","doi-asserted-by":"crossref","first-page":"e202451437","DOI":"10.1002\/eji.202451437","article-title":"JAK inhibitors and b cell function: a comparative study of their impact on plasma cell differentiation, cytokine production, and naive B cell activation","volume":"55","author":"Huang","year":"2025","journal-title":"Eur J Immunol"},{"key":"2026032505580851200_jjag028-B16","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s00018-024-05196-1","article-title":"Macrophage re-programming by JAK inhibitors relies on MAFB","volume":"81","author":"Lopez-Navarro","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"2026032505580851200_jjag028-B17","doi-asserted-by":"crossref","first-page":"e11761","DOI":"10.1002\/acr2.11761","article-title":"Whole-blood RNA sequencing profiling of patients with rheumatoid arthritis treated with tofacitinib","volume":"7","author":"Bellocchi","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"2026032505580851200_jjag028-B18","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/ni1254","article-title":"Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages","volume":"6","author":"Harrington","year":"2005","journal-title":"Nat Immunol"},{"key":"2026032505580851200_jjag028-B19","doi-asserted-by":"crossref","first-page":"e0285918","DOI":"10.1371\/journal.pone.0285918","article-title":"Colonic mucosal associated invariant T cells in Crohn\u2019s disease have a diverse and non-public T cell receptor beta chain repertoire","volume":"18","author":"Konecny","year":"2023","journal-title":"PLoS One"},{"key":"2026032505580851200_jjag028-B20","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1084\/jem.20101712","article-title":"IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease","volume":"208","author":"Geremia","year":"2011","journal-title":"J Exp Med"},{"key":"2026032505580851200_jjag028-B21","doi-asserted-by":"crossref","first-page":"4662","DOI":"10.4049\/jimmunol.177.7.4662","article-title":"IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection","volume":"177","author":"Lockhart","year":"2006","journal-title":"J Immunol"},{"key":"2026032505580851200_jjag028-B22","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/ibd\/izad224","article-title":"Vedolizumab efficacy is associated with decreased intracolonic dendritic cells, not memory T cells","volume":"30","author":"Boden","year":"2024","journal-title":"Inflamm Bowel Dis"},{"key":"2026032505580851200_jjag028-B23","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41467-024-45665-6","article-title":"Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis","volume":"15","author":"Mennillo","year":"2024","journal-title":"Nat Commun"},{"key":"2026032505580851200_jjag028-B24","doi-asserted-by":"crossref","first-page":"eadg7549","DOI":"10.1126\/sciimmunol.adg7549","article-title":"Gut-associated lymphoid tissue attrition associates with response to anti-alpha4beta7 therapy in ulcerative colitis","volume":"9","author":"Canales-Herrerias","year":"2024","journal-title":"Sci Immunol"},{"key":"2026032505580851200_jjag028-B25","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1053\/j.gastro.2021.02.019","article-title":"Identification of an anti-integrin alphavbeta6 autoantibody in patients with ulcerative colitis","volume":"160","author":"Kuwada","year":"2021","journal-title":"Gastroenterology"},{"key":"2026032505580851200_jjag028-B26","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1053\/j.gastro.2022.06.026","article-title":"Anti-integrin alphavbeta6 antibody as a diagnostic marker for pediatric patients with ulcerative colitis","volume":"163","author":"Muramoto","year":"2022","journal-title":"Gastroenterology"},{"key":"2026032505580851200_jjag028-B27","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11071881","article-title":"Measurement of serum IgG anti-integrin alphavbeta6 autoantibodies is a promising tool in the diagnosis of ulcerative colitis","volume":"11","author":"Rydell","year":"2022","journal-title":"J Clin Med"},{"key":"2026032505580851200_jjag028-B28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s00535-024-02176-x","article-title":"Anti-integrin alphavbeta6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study","volume":"60","author":"Okabe","year":"2025","journal-title":"J Gastroenterol"},{"key":"2026032505580851200_jjag028-B29","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1053\/j.gastro.2022.12.042","article-title":"Anti-integrin alphavbeta6 autoantibodies are a novel biomarker that antedate ulcerative colitis","volume":"164","author":"Livanos","year":"2023","journal-title":"Gastroenterology"},{"key":"2026032505580851200_jjag028-B30","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ejcb.2008.01.012","article-title":"Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship","volume":"87","author":"Wipff","year":"2008","journal-title":"Eur J Cell Biol"},{"key":"2026032505580851200_jjag028-B31","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1056\/NEJMc2508023","article-title":"CD19 CAR T-cell therapy in multidrug-resistant ulcerative colitis","volume":"393","author":"Muller","year":"2025","journal-title":"N Engl J Med"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/3\/jjag028\/67507491\/jjag028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/3\/jjag028\/67507491\/jjag028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:58:16Z","timestamp":1774432696000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/doi\/10.1093\/ecco-jcc\/jjag028\/8540151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,10]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjag028","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,3]]},"article-number":"jjag028"}}