Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells.

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.