BCL6 corepressor contributes to Th17 cell formation by inhibiting Th17 fate suppressors

Autor: Jonathan L. Linehan, Dmitri I. Kotov, Marc K. Jenkins, Jessica A. Kotov, Micah D. Gearhart, Vivian J. Bardwell
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Jumonji Domain-Containing Histone Demethylases
Streptococcus pyogenes
medicine.medical_treatment
Immunology
chemical and pharmacologic phenomena
Article
03 medical and health sciences
0302 clinical medicine
RAR-related orphan receptor gamma
medicine
Animals
Immunology and Allergy
Cell Lineage
Receptor
Transcription factor
Research Articles
Chemistry
F-Box Proteins
T-cell receptor
hemic and immune systems
Cell Differentiation
Lymphocyte Subsets
3. Good health
Cell biology
Mice
Inbred C57BL
Repressor Proteins
RUNX2
030104 developmental biology
Cytokine
Gene Expression Regulation
CpG site
Proto-Oncogene Proteins c-bcl-6
Cytokines
Th17 Cells
Female
Receptors
Chemokine
CRISPR-Cas Systems
Co-Repressor Proteins
Chromatin immunoprecipitation
Signal Transduction
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20182376
Popis: Th17 cells provide a protective immunity against extracellular bacterial and fungal pathogens. Kotov et al. identify and characterize a mechanism by which BCOR promotes Th17 formation after Streptococcus pyogenes infection by repressing genes that inhibit the Th17 lineage.
CD4+ T helper 17 (Th17) cells protect vertebrate hosts from extracellular pathogens at mucosal surfaces. Th17 cells form from naive precursors when signals from the T cell antigen receptor (TCR) and certain cytokine receptors induce the expression of the RORγt transcription factor, which activates a set of Th17-specific genes. Using T cell–specific loss-of-function experiments, we find that two components of the Polycomb repressive complex 1.1 (PRC1.1), BCL6 corepressor (BCOR) and KDM2B, which helps target the complex to unmethylated CpG DNA islands, are required for optimal Th17 cell formation in mice after Streptococcus pyogenes infection. Genome-wide expression and BCOR chromatin immunoprecipitation studies revealed that BCOR directly represses Lef1, Runx2, and Dusp4, whose products inhibit Th17 differentiation. Together, the results suggest that the PRC1.1 components BCOR and KDM2B work together to enhance Th17 cell formation by repressing Th17 fate suppressors.
Databáze: OpenAIRE
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