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Activated HLA-DR+CD38+ Effector Th1/17 Cells Distinguish Crohn's Disease-associated Perianal Fistulas from Cryptoglandular Fistulas.
Ouboter, Laura F; Lindelauf, Ciska; Jiang, Qinyue; Schreurs, Mette; Abdelaal, Tamim R; Luk, Sietse J; Barnhoorn, Marieke C; Hueting, Willem E; Han-Geurts, Ingrid J; Peeters, Koen C M J; Holman, Fabian A; Koning, Frits; van der Meulen-de Jong, Andrea E; Pascutti, Maria Fernanda.
Afiliación
  • Ouboter LF; Department of Gastroenterology and Hepatology, 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 Immunology, Leiden University Medical Center, Leiden, the Netherlands.
  • Luk SJ; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Barnhoorn MC; Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands.
  • Hueting WE; Systems and Biomedical Engineering Department, Faculty of Engineering Cairo University, Giza, Egypt.
  • Han-Geurts IJ; Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
  • Peeters KCMJ; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
  • Holman FA; Department of Surgery, Alrijne hospital, Leiderdorp, the Netherlands.
  • Koning F; Department of Surgery, Proctos Clinic, Bilthoven, the Netherlands.
  • van der Meulen-de Jong AE; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
  • Pascutti MF; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Inflamm Bowel Dis ; 30(11): 2146-2161, 2024 Nov 04.
Article en En | MEDLINE | ID: mdl-38776553
ABSTRACT

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.
We applied high-dimensional analyses to profile the immune compartment in CD-associated and cryptoglandular perianal fistulas. Data analysis revealed activated HLA-DR+CD38+ effector Th1/17 cells as distinctly increased in CD-associated fistulas, suggesting a potential novel therapeutic target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Crohn / Antígenos HLA-DR / Fístula Rectal / Células TH1 / Células Th17 Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Inflamm Bowel Dis Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Crohn / Antígenos HLA-DR / Fístula Rectal / Células TH1 / Células Th17 Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Inflamm Bowel Dis Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido