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Title: Inhibition of stearoyl‐CoA desaturases suppresses follicular help T‐ and germinal center B‐ cell responses
Abstract

Stearoyl‐CoA desaturases (SCD) are endoplasmic reticulum (ER)‐associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4+T‐helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (TFH) cells express higher levels of SCD compared to non‐TFHcells. Further, the expression of SCD in TFHcells is dependent on the TFHlineage‐specification transcription factor BCL6. We found that the inhibition of SCD impaired TFHcell maintenance and shifted the balance between TFHand follicular regulatory T (TFR) cells in the spleen. Consequently, SCD inhibition dampened germinal center B‐cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced TFHcell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.

 
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NSF-PAR ID:
10455842
Author(s) / Creator(s):
 ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
European Journal of Immunology
Volume:
50
Issue:
7
ISSN:
0014-2980
Page Range / eLocation ID:
p. 1067-1077
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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