Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation
- Australian National University, Australia
- Baker IDI Heart and Diabetes Institute, Australia
- Walter and Eliza Hall Institute of Medical Research, Australia
- McGill University, Canada
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 α1 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.
Article and author information
Author details
Reviewing Editor
- Shimon Sakaguchi, Osaka University, Japan
Ethics
Animal experimentation: Animal experiments were approved by the Animal Experimentation Ethics Committee of the Australian National University (Protocols J.IG.71.08 and A2012/05) and the McGill University Ethics Committee (Protocol 7259). Mice were maintained in a specific germ-free environment.
Version history
- Received: May 13, 2015
- Accepted: October 22, 2015
- Accepted Manuscript published: October 23, 2015 (version 1)
- Version of Record published: December 31, 2015 (version 2)
Copyright
© 2015, Ramiscal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation
eLife 4:e08698.
https://doi.org/10.7554/eLife.08698
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