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

Laura F Ouboter1,2, Ciska Lindelauf2, Qinyue Jiang2

  • 1Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.

Inflammatory Bowel Diseases
|May 22, 2024
PubMed

Insights

Activated CD4+ T cells with a Th1/17 phenotype are enriched in Crohn's disease (CD) fistulas, distinguishing them from non-CD fistulas. These cells may serve as biomarkers and therapeutic targets for CD-associated perianal fistulas.

Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Perianal fistulas are a common and debilitating complication of Crohn's disease (CD).
  • CD-associated fistulas are often more challenging to treat than non-CD (cryptoglandular) fistulas.
  • Understanding the immune cell landscape is crucial for developing effective therapies for CD-associated fistulas.

Purpose of the Study:

  • To characterize the immune cell composition and spatial localization in CD-associated and cryptoglandular perianal fistulas.
  • To identify distinct immune cell populations that differentiate between these two fistula types.
  • To explore potential biomarkers and therapeutic targets for CD-associated fistulas.

Main Methods:

  • High-dimensional analyses including single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC).
  • Profiling of immune cells in explanted fistula tissues and blood samples from patients with CD-associated and cryptoglandular fistulas.
  • Comprehensive phenotyping and spatial distribution analysis of immune cell subsets.

Main Results:

  • Activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated fistulas compared to cryptoglandular fistulas.
  • These enriched T cells exhibited features of proliferation, regulation, and differentiation.
  • These specific CD4+ T cells were also found in the blood and colocalized with B cells and macrophages within the fistula tracts.

Conclusions:

  • Proliferating, activated HLA-DR+CD38+ effector Th1/17 cells are a key feature distinguishing CD-associated from cryptoglandular perianal fistulas.
  • These cells represent a promising blood biomarker for discriminating between the two fistula types.
  • Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a novel therapeutic strategy for managing CD-related fistulas.
Abstract

Keywords:
Crohn’s diseasehigh-dimensional analysesperianal fistulas

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