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Related Concept Videos

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Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
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Human small intestine contains 2 functionally distinct regulatory T-cell subsets.

Sudhir Kumar Chauhan1, Raquel Bartolomé Casado2, Ole J B Landsverk3

  • 1Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

The Journal of Allergy and Clinical Immunology
|March 9, 2023
PubMed
Summary

Human gut regulatory T (Treg) cells have two distinct subsets. These Treg cells are rare in healthy individuals but significantly increase in active celiac disease, impacting immune responses.

Keywords:
CD4 T cellsFoxp3HeliosRegulatory T (Treg) cellsceliac diseasehuman small intestinetransplantation

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Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Regulatory T (Treg) CD4 cells in the mouse gut are crucial for immune tolerance to dietary antigens and microbiota.
  • Limited data exists on the phenotype and function of Treg cells within the human gut.

Purpose of the Study:

  • To comprehensively characterize Foxp3+ CD4 Treg cells in the human small intestine (SI).
  • To compare Treg cells from normal SI, transplanted duodenal tissue, and celiac disease lesions.

Main Methods:

  • Detailed immunophenotyping of Treg cells and conventional CD4 T cells from the human SI.
  • Assessment of Treg cell suppressive activity and cytokine production.
  • Analysis of Helios expression within Treg cell subsets.

Main Results:

  • Human SI Treg cells (Foxp3+ CD4) were CD45RA-CD127-CTLA-4+ and suppressed T cell proliferation.
  • Approximately 60% of Treg cells expressed Helios; Helios-negative Treg cells produced IL-17, IFN-γ, and IL-10 upon stimulation.
  • Donor Helios-negative Treg cells persisted for at least 1 year post-transplantation.
  • In active celiac disease, both Helios-negative and Helios-positive Treg cell subsets expanded significantly (5- to 10-fold) compared to normal SI (2% of CD4 T cells).

Conclusions:

  • The human small intestine harbors two distinct subsets of Treg cells with differing phenotypes and functions.
  • These Treg cell subsets are infrequent in healthy individuals but markedly increase during active celiac disease.