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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
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Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells.

Paola Gruarin1, Stefano Maglie1, Marco De Simone1

  • 1INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.

European Journal of Immunology
|November 16, 2018
PubMed
Summary

Eomesodermin (Eomes) defines a unique human CD4+ T cell subset that produces both IFN-γ and IL-10. These Eomes+ Tr1-like cells are distinct and found in various tissues, with altered frequencies in inflammatory diseases.

Keywords:
DifferentiationEOMESGranzyme KRegulatory T cellsTh17

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The lineage identity of human IL-10-producing regulatory T cells (Tr1) is debated.
  • Understanding Tr1 cell differentiation is crucial for immune regulation.

Purpose of the Study:

  • To investigate the role of Eomesodermin (Eomes) in defining human Tr1-like cells.
  • To characterize the unique features and functions of Eomes-expressing CD4+ T cells.

Main Methods:

  • Flow cytometry and gene expression analysis of human CD4+ T cell subsets.
  • Investigation of transcription factor roles in T cell differentiation.
  • Analysis of T cell populations in patients with inflammatory diseases.

Main Results:

  • Eomesodermin (Eomes) acts as a lineage-defining transcription factor for human IFN-γ/IL-10 co-producing Tr1-like cells.
  • These Eomes+ Tr1-like cells are distinct from other CD4+ T cell subsets, expressing Granzyme K and lacking CD40L and IL-7R.
  • Eomes antagonizes Th17 fate and controls IFN-γ and Granzyme K expression, while IL-10 regulation differs from mice.
  • Myeloid dendritic cells and IL-27 promote Tr1-like cell generation.
  • Eomes+ CD4+ T cells are present in various tissues and altered in inflammatory bowel disease and graft-versus-host disease.

Conclusions:

  • Eomesodermin (Eomes) identifies a unique effector CD4+ T cell subset (Tr1-like cells) characterized by Granzyme K expression.
  • These cells represent a distinct lineage with significant implications for immune responses and inflammatory conditions.