edoc

The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity

Heinz, Leonhard X. and Baumann, Christoph L. and Köberlin, Marielle S. and Snijder, Berend and Gawish, Riem and Shui, Guanghou and Sharif, Omar and Aspalter, Irene M. and Müller, André C. and Kandasamy, Richard K. and Breitwieser, Florian P. and Pichlmair, Andreas and Bruckner, Manuela and Rebsamen, Manuele and Blüml, Stephan and Karonitsch, Thomas and Fauster, Astrid and Colinge, Jacques and Bennett, Keiryn L. and Knapp, Sylvia and Wenk, Markus R. and Superti-Furga, Giulio. (2015) The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity. Cell reports, Vol. 11, H. 12. pp. 1919-1928.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6419750

Downloads: Statistics Overview

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Wenk, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:2211-1247
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:06 Nov 2015 10:21
Deposited On:06 Nov 2015 10:21

Repository Staff Only: item control page