BCL6 represses antiviral resistance in follicular T helper cells

Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K. Gupta, Alexander L. Dent, Luis J. Montaner, Qigui Yu, Jie Sun

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells. A lower antiviral resistance in Tfh was consistent with a higher susceptibility to retroviral infections. Mechanisti-cally, we found that BCL6, a master regulator of Tfh cell development, binds to ISG loci and inhibits the expression of MX2 and IFITM3 in Tfh cells. We demonstrate further that inhibition of the BCL6 BR-C, ttk, and bab (BTB) domain function increases the expression of ISGs and suppresses HIV infection and replication in Tfh cells. Our data reveal a regulatory role of BCL6 in inhibiting antiviral resistance factors in Tfh cells, thereby promoting the susceptibility Tfh cells to viral infections. Our results indicate that the modulation of BCL6 function in Tfh cells could be a potential strategy to enhance Tfh cell resistance to retroviral infections and potentially decrease cellular reservoirs of HIV infection.

Original languageEnglish (US)
Pages (from-to)527-536
Number of pages10
JournalJournal of Leukocyte Biology
Volume102
Issue number2
DOIs
StatePublished - Aug 2017

Keywords

  • HIV infection
  • IFITM3
  • MX2
  • Tfh cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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