| First Author | Ramiscal RR | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 26496200 | Mgi Jnum | J:229554 |
| Mgi Id | MGI:5752435 | Doi | 10.7554/eLife.08698 |
| Citation | Ramiscal RR, et al. (2015) Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation. Elife 4:e08698 |
| abstractText | 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. |
