Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation
- Author(s)
- Ramiscal, RR; Parish, IA; Lee-Young, RS; Babon, JJ; Blagih, J; Pratama, A; Martin, J; Hawley, N; Cappello, JY; Nieto, PF; Ellyard, J; Kershaw, NJ; Sweet, RA; Goodnow, CC; Jones, RG; Febbraio, MA; Vinuesa, C; Athanasopoulos, V;
- Journal Title
- Elife
- Publication Type
- Journal Article
- Abstract
- T follicular helper cells (Tfh) are critical for the longevity and quality of antibody-mediated protection against infection. Yet few signaling pathways have been identified to be unique solely to Tfh development. ROQUIN is a post-transcriptional repressor of T cells, acting through its ROQ domain to destabilize mRNA targets important for Th1, Th17 and Tfh biology. Here, we report that ROQUIN has a paradoxical function on Tfh differentiation mediated by its RING domain: mice with a T cell-specific deletion of the ROQUIN RING domain have unchanged Th1, Th2, Th17 and Tregs during a T-dependent response, but show a profoundly defective antigen-specific Tfh compartment. ROQUIN RING signaling directly antagonized the catalytic alpha1 subunit of Adenosine Monophosphate-activated Protein Kinase (AMPK), a central stress-responsive regulator of cellular metabolism and mTOR signaling, which is known to facilitate T-dependent humoral immunity. We therefore unexpectedly uncover a ROQUIN-AMPK metabolic signaling nexus essential for selectively promoting Tfh responses.
- Publisher
- eLife Sciences Publications
- Research Division(s)
- Structural Biology
- PubMed ID
- 26496200
- Publisher's Version
- https://doi.org/10.7554/eLife.08698
- Open Access at Publisher's Site
http://elifesciences.org/content/early/2015/10/23/eLife.08698- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-10-28 01:52:45
Last Modified: 2016-01-13 10:03:25