Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function.

FOXP3 regulatory T cells (Treg cells) are key for immune homeostasis. Here, we reveal that nuclear receptor corepressor 1 (NCOR1) controls naïve and effector Treg cell states. Upon NCOR1 deletion in T cells, effector Treg cell frequencies were elevated in mice and in in vitro-generated human Treg cells.

Histone deacetylase 1 controls CD4 T cell trafficking in autoinflammatory diseases.

CD4 T cell trafficking is a fundamental property of adaptive immunity. In this study, we uncover a novel role for histone deacetylase 1 (HDAC1) in controlling effector CD4 T cell migration, thereby providing mechanistic insight into why a T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis (EAE). HDAC1-deficient CD4 T cells downregulated genes associated with leukocyte extravasation.

NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4 T Cells.

The differentiation of naïve CD4 T cells into T helper (Th) subsets is key for a functional immune response and has to be tightly controlled by transcriptional and epigenetic processes. However, the function of cofactors that connect gene-specific transcription factors with repressive chromatin-modifying enzymes in Th cells is yet unknown. Here we demonstrate an essential role for nuclear receptor corepressor 1 (NCOR1) in regulating naïve CD4 T cell and Th1/Th17 effector transcriptomes.

Histone deacetylases 1 and 2 restrain CD4+ cytotoxic T lymphocyte differentiation.

Some effector CD4+ T cell subsets display cytotoxic activity, thus breaking the functional dichotomy of CD4+ helper and CD8+ cytotoxic T lymphocytes. However, molecular mechanisms regulating CD4+ cytotoxic T lymphocyte (CD4+ CTL) differentiation are poorly understood. Here we show that levels of histone deacetylases 1 and 2 (HDAC1-HDAC2) are key determinants of CD4+ CTL differentiation.

Aryl hydrocarbon receptor activation inhibits in vitro differentiation of human monocytes and Langerhans dendritic cells.

The transcription factor aryl hydrocarbon receptor (AhR) represents a promising therapeutic target in allergy and autoimmunity. AhR signaling induced by the newly described ligand VAF347 inhibits allergic lung inflammation as well as suppresses pancreatic islet allograft rejection. These effects are likely mediated via alterations in dendritic cell (DC) function.