Pré-Publication, Document De Travail Année : 2024

Fine-Tuning Levels of Filamins A and B as a Specific Mechanism Sustaining Th2 Lymphocyte Functions

Arun Subramaniam
  • Fonction : Auteur

Résumé

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 unravel 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 α V β 3 integrin-dependent cell migration. Genes encoding the α V β 3 integrin and ASB2α belong to the core of Th2-specific genes. Using genetically modified mice or the small molecule thiostrepton, 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 rewire Th2 lymphocyte-mediated responses.

HAL

Cite hal-04822173 Article Kilian Maire, Léa Chamy, Samira Ghazali, Manon Carratala-Lasserre, Margot Zahm, et al.. Fine-tuning levels of filamins a and b as a specific mechanism sustaining Th2 lymphocyte functions. Nature Communications, 2024, 15 (1), pp.10574. ⟨10.1038/s41467-024-53768-3⟩. ⟨hal-04822173⟩

Dates et versions

hal-04791313 , version 1 (19-11-2024)

Identifiants

Citer

Kilian Maire, Samira Ghazali, Manon Carratala-Lasserre, Margot Zahm, Clément Bouisset, et al.. Fine-Tuning Levels of Filamins A and B as a Specific Mechanism Sustaining Th2 Lymphocyte Functions. 2024. ⟨hal-04791313⟩
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