The RNA binding protein Sam68 controls T helper 1 differentiation and anti-mycobacterial response through modulation of miR-29.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
29
03
2018
accepted:
27
08
2018
revised:
08
08
2018
pubmed:
28
9
2018
medline:
2
10
2020
entrez:
28
9
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30258098
doi: 10.1038/s41418-018-0201-9
pii: 10.1038/s41418-018-0201-9
pmc: PMC6748099
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cytokines
0
Khdrbs1 protein, mouse
0
MIRN29 microRNA, mouse
0
MicroRNAs
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1169-1180Références
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