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.
journal_name
Elifejournal_title
eLifeauthors
Ramiscal RR,Parish IA,Lee-Young RS,Babon JJ,Blagih J,Pratama A,Martin J,Hawley N,Cappello JY,Nieto PF,Ellyard JI,Kershaw NJ,Sweet RA,Goodnow CC,Jones RG,Febbraio MA,Vinuesa CG,Athanasopoulos Vdoi
10.7554/eLife.08698subject
Has Abstractpub_date
2015-10-23 00:00:00issn
2050-084Xjournal_volume
4pub_type
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