TY - JOUR
T1 - Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity
AU - Grajchen, Elien
AU - Loix, Melanie
AU - Baeten, Paulien
AU - Côrte-Real, Beatriz F.
AU - Hamad, Ibrahim
AU - Vanherle, Sam
AU - Haidar, Mansour
AU - Dehairs, Jonas
AU - Broos, Jelle Y.
AU - Ntambi, James M.
AU - Zimmermann, Robert
AU - Breinbauer, Rolf
AU - Stinissen, Piet
AU - Hellings, Niels
AU - Verberk, Sanne G.S.
AU - Kooij, Gijs
AU - Giera, Martin
AU - Swinnen, Johannes V.
AU - Broux, Bieke
AU - Kleinewietfeld, Markus
AU - Hendriks, Jerome J.A.
AU - Bogie, Jeroen F.J.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.
AB - The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.
KW - Autoimmunity
KW - Fatty acid metabolism
KW - Multiple sclerosis
KW - Regulatory T cells
KW - Stearoyl-CoA desaturase-1
UR - http://www.scopus.com/inward/record.url?scp=85152394645&partnerID=8YFLogxK
U2 - 10.1038/s41423-023-01011-2
DO - 10.1038/s41423-023-01011-2
M3 - Article
C2 - 37041314
AN - SCOPUS:85152394645
SN - 1672-7681
VL - 20
SP - 666
EP - 679
JO - Cellular and Molecular Immunology
JF - Cellular and Molecular Immunology
IS - 6
ER -