The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity

Abstract : Lipid metabolism and receptor-mediated signaling are highly intertwined processes that cooperate to fulfill cellular functions and safeguard cellular homeostasis. Activation of Toll-like receptors (TLRs) leads to a complex cellular response, orchestrating a diverse range of inflammatory events that need to be tightly controlled. Here, we identified the GPI-anchored Sphingomyelin Phosphodiesterase, Acid-Like 3B (SMPDL3B) in a mass spectrometry screening campaign for membrane proteins co-purifying with TLRs. Deficiency of Smpdl3b in macrophages enhanced responsiveness to TLR stimulation and profoundly changed the cellular lipid composition and membrane fluidity. Increased cellular responses could be reverted by re-introducing affected ceramides, functionally linking membrane lipid composition and innate immune signaling. Finally, Smpdl3b-deficient mice displayed an intensified inflammatory response in TLR-dependent peritonitis models, establishing its negative regulatory role in vivo. Taken together, our results identify the membrane-modulating enzyme SMPDL3B as a negative regulator of TLR signaling that functions at the interface of membrane biology and innate immunity.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [48 références]  Voir  Masquer  Télécharger

https://hal.umontpellier.fr/hal-02285811
Contributeur : Mélanie Karli <>
Soumis le : vendredi 13 septembre 2019 - 10:22:36
Dernière modification le : mardi 17 septembre 2019 - 11:24:54

Fichier

1-s2.0-S2211124715005045-main....
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Leonhard x. Heinz, Christoph l. Baumann, Marielle s. Köberlin, Berend Snijder, Riem Gawish, et al.. The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity. Cell Reports , Elsevier Inc, 2015, 11 (12), pp.1919-1928. ⟨10.1016/j.celrep.2015.05.006⟩. ⟨hal-02285811⟩

Partager

Métriques

Consultations de la notice

29

Téléchargements de fichiers

45