Inhibition of stearoyl-CoA desaturases suppresses follicular help T- and germinal center B- cell responses

Young Min Son, In Su Cheon, Nick P. Goplen, Alexander L. Dent, Jie Sun

Research output: Contribution to journalArticle

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-TFH cells. Further, the expression of SCD in TFH cells is dependent on the TFH lineage-specification transcription factor BCL6. We found that the inhibition of SCD impaired TFH cell maintenance and shifted the balance between TFH and 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 TFH 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.

Original languageEnglish (US)
Pages (from-to)1067-1077
Number of pages11
JournalEuropean Journal of Immunology
Volume50
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • Endoplasmic reticulum stress
  • Follicular help T cells
  • Germinal center B cells
  • Lipid metabolism
  • Stearoyl-CoA desaturase 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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