1. Fine-tuning levels of filamins a and b as a specific mechanism sustaining Th2 lymphocyte functions
- Author
-
Kilian Maire, Léa Chamy, Samira Ghazali, Manon Carratala-Lasserre, Margot Zahm, Clément Bouisset, Arnaud Métais, Lucie Combes-Soia, Lidia de la Fuente-Vizuete, Hussein Trad, Adeline Chaubet, Magali Savignac, Anne Gonzalez de Peredo, Arun Subramaniam, Olivier Joffre, Pierre G. Lutz, and Isabelle Lamsoul
- Subjects
Science - Abstract
Abstract Augmenting the portfolio of therapeutics for type 2-driven diseases is crucial to address unmet clinical needs and to design personalized treatment schemes. An attractive therapy for such diseases would consist in targeting the recruitment of T helper 2 (Th2) lymphocytes to inflammatory sites. Herein, we show the degradation of filamins (FLN) a and b by the ASB2α E3 ubiquitin ligase as a mechanism sustaining Th2 lymphocyte functions. Low levels of FLNa and FLNb confer an elongated shape to Th2 lymphocytes associated with efficient αVβ3 integrin-dependent cell migration. Genes encoding the αVβ3 integrin and ASB2α belong to the core of Th2-specific genes. Using genetically modified mice, we find that increasing the levels of FLNa and FLNb in Th2 lymphocytes reduces airway inflammation through diminished Th2 lymphocyte recruitment in inflamed lungs. Collectively, our results highlight ASB2α and its substrates FLNa and FLNb to alter Th2 lymphocyte-mediated responses.
- Published
- 2024
- Full Text
- View/download PDF