Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation

Roybel R Ramiscal, Ian A Parish, Robert S. Lee-Young, Jeffrey Babon, Julianna Blagih, Alvin Pratama, Jaime L Martin, Naomi Hawley, Jean Y. Cappello, Pablo F. Nieto, Julia I Ellyard, Nadia J Kershaw, Rebecca A. Sweet, Christopher C Goodnow, Russell G. Jones, Mark A. Febbraio, Carola G Vinuesa, Vicki Athanasopoulos

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)


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 a1 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.

Original languageEnglish
Article numbere08698
Number of pages22
Publication statusPublished - 23 Oct 2015
Externally publishedYes

Cite this