| Added by | mollevi |
|---|---|
| Last modified by | jacques.colinge |
| Group name | EquipeJC |
| Item Type | Journal Article |
| Title | The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity |
| Creator | Heinz et al. |
| Author | L. X. Heinz |
| Author | C. L. Baumann |
| Author | M. S. Koberlin |
| Author | B. Snijder |
| Author | R. Gawish |
| Author | G. Shui |
| Author | O. Sharif |
| Author | I. M. Aspalter |
| Author | A. C. Muller |
| Author | R. K. Kandasamy |
| Author | F. P. Breitwieser |
| Author | A. Pichlmair |
| Author | M. Bruckner |
| Author | M. Rebsamen |
| Author | S. Bluml |
| Author | T. Karonitsch |
| Author | A. Fauster |
| Author | J. Colinge |
| Author | K. L. Bennett |
| Author | S. Knapp |
| Author | M. R. Wenk |
| Author | G. Superti-Furga |
| 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. |
| Publication | Cell Rep |
| Volume | 11 |
| Pages | 1919-28 |
| Date | Jun 30 2015 |
| Journal Abbr | Cell reports |
| DOI | 10.1016/j.celrep.2015.05.006 |
| ISSN | 2211-1247 (Electronic) |
| Tags | original, phd |
| Date Added | 2018/11/14 - 11:48:35 |
| Date Modified | 2019/10/22 - 21:16:49 |
| Notes and Attachments | (Note) (Note) 26095358 (Attachment) |
Institut de Recherche en Cancérologie de
