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

Jessica A. Kotov, Dmitri I. Kotov, Jonathan L. Linehan, Vivian J Bardwell, Micah D Gearhart, Marc K. Jenkins

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1450-1464
Number of pages15
JournalJournal of Experimental Medicine
Volume216
Issue number6
DOIs
StatePublished - Jun 1 2019

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (grants R01 AI039614, R01 AI103760, and R37 AI027998 to M.K. Jenkins; grants T32 AI007313 and F31 AI133716 to J.A. Kotov; grants T32 AI83196 and T32 AI007313 to D.I. Kotov; and grants R01 CA071540 and R01 HD084459 to V.J. Bardwell). This work was also supported by the University of Minnesota Microbiology and Immunology Department (Dennis W. Watson Fellowship to J.A. Kotov). The authors declare no competing financial interests.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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