Cargando…

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

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramiscal, Roybel R, Parish, Ian A, Lee-Young, Robert S, Babon, Jeffrey J, Blagih, Julianna, Pratama, Alvin, Martin, Jaime, Hawley, Naomi, Cappello, Jean Y, Nieto, Pablo F, Ellyard, Julia I, Kershaw, Nadia J, Sweet, Rebecca A, Goodnow, Christopher C, Jones, Russell G, Febbraio, Mark A, Vinuesa, Carola G, Athanasopoulos, Vicki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716841/
https://www.ncbi.nlm.nih.gov/pubmed/26496200
http://dx.doi.org/10.7554/eLife.08698
Descripción
Sumario: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. DOI: http://dx.doi.org/10.7554/eLife.08698.001