Activated HLA-DR+CD38+ Effector Th1/17 Cells Distinguish Crohn's Disease-associated Perianal Fistulas from Cryptoglandular Fistulas.

Autor:	Ouboter LF; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., Lindelauf C; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., Jiang Q; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., Schreurs M; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., Abdelaal TR; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.; Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands.; Systems and Biomedical Engineering Department, Faculty of Engineering Cairo University, Giza, Egypt., Luk SJ; Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands., Barnhoorn MC; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands., Hueting WE; Department of Surgery, Alrijne hospital, Leiderdorp, the Netherlands., Han-Geurts IJ; Department of Surgery, Proctos Clinic, Bilthoven, the Netherlands., Peeters KCMJ; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands., Holman FA; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands., Koning F; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., van der Meulen-de Jong AE; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands., Pascutti MF; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Jazyk:	angličtina
Zdroj:	Inflammatory bowel diseases [Inflamm Bowel Dis] 2024 May 22. Date of Electronic Publication: 2024 May 22.
DOI:	10.1093/ibd/izae103
Abstrakt:	Background: Perianal fistulas are a debilitating complication of Crohn's 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. Methods: 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 = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets. Results: 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. Conclusions: 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. (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)
Databáze:	MEDLINE
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