The RNA binding protein Sam68 controls T helper 1 differentiation and anti-mycobacterial response through modulation of miR-29

Claudio Sette, Davide Bonvissuto, Elisabetta Volpe, Neri Mercatelli, Rosella Cicconi, Marco De Bardi, Alessia Capone, Maurizio Fraziano, Maurizio Mattei, Luca Battistini, Maria Paola Paronetto

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)

Abstract

Polarization of naive T cells into interferon (IFN)-γ-producing T helper 1 (Th1) cells is an essential event in the inflammatory response to pathogens. Herein, we identify the RNA binding protein Sam68 as a specific modulator of Th1 differentiation. Sam68-knockout (ko) naive T cells are strongly defective in IL-12-mediated Th1 polarization and express low levels of T-bet and Eomes. Consequently, Sam68-ko Th1 cells are significantly impaired in IFN-γ production. Moreover, we found that Sam68 is required for the induction of an inflammatory Th1 response during Mycobacterium bovis Bacillus Calmette–Guerin (BCG) infection, thus limiting bacterial dissemination in the lungs. Mechanistically, Sam68 directly binds to the microRNA miR-29, a negative regulator of Th1 response, and inhibits its expression during BCG infection. These findings uncover a novel post-transcriptional mechanism required for the Th1-mediated defense against intracellular pathogens and identify a new function for Sam68 in the regulation of the immune response.
Lingua originaleEnglish
pagine (da-a)1169-1180
RivistaCell Death and Differentiation
Volume26
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Cell Biology
  • Molecular Biology

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