{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:49:44Z","timestamp":1790804984740,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Perianal fistulas are a debilitating complication of Crohn\u2019s disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n =\u200510; non-CD fistula, n =\u20055) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n\u2005=\u200510; non-CD, n\u2005=\u200511) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n\u2005=\u20055) to investigate the spatial distribution\/interaction of relevant immune cell subsets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1\/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Overall, proliferating activated HLA-DR+CD38+ effector Th1\/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izae103","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T21:28:48Z","timestamp":1716413328000},"page":"2146-2161","source":"Crossref","is-referenced-by-count":7,"title":["Activated HLA-DR+CD38+ Effector Th1\/17 Cells Distinguish Crohn\u2019s Disease-associated Perianal Fistulas from Cryptoglandular Fistulas"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-5644","authenticated-orcid":false,"given":"Laura F","family":"Ouboter","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]},{"name":"Department of Immunology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciska","family":"Lindelauf","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Schreurs","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamim R","family":"Abdelaal","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]},{"name":"Bioinformatics Lab, Delft University of Technology , Delft ,","place":["the Netherlands"]},{"name":"Systems and Biomedical Engineering Department, Faculty of Engineering Cairo University , Giza ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sietse J","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke C","family":"Barnhoorn","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem E","family":"Hueting","sequence":"additional","affiliation":[{"name":"Department of Surgery, Alrijne hospital , Leiderdorp ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid J","family":"Han-Geurts","sequence":"additional","affiliation":[{"name":"Department of Surgery, Proctos Clinic , Bilthoven ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen C M J","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian A","family":"Holman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E","family":"van der Meulen-de 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