Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 50, Issue 7, Pages 1067-1077Publisher
WILEY
DOI: 10.1002/eji.201948257
Keywords
Endoplasmic reticulum stress; Follicular help T cells; Germinal center B cells; Lipid metabolism; Stearoyl-CoA desaturase 1
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Funding
- National Science Foundation Funding Source: Medline
- NHLBI NIH HHS [R01 HL126647] Funding Source: Medline
- NIAID NIH HHS [R01 AI147394, R01 AI132771] Funding Source: Medline
- NIA NIH HHS [T32 AG049672, R01 AG047156] Funding Source: Medline
- US National Institutes of Health [AI147394] Funding Source: Medline
- Kogod Aging Center Funding Source: Medline
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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.
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