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 (T-FH) cells express higher levels of SCD compared to non-T(FH)cells. Further, the expression of SCD in T(FH)cells is dependent on the T(FH)lineage-specification transcription factor BCL6. We found that the inhibition of SCD impaired T(FH)cell maintenance and shifted the balance between T(FH)and follicular regulatory T (T-FR) 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 T(FH)cell 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.