Deficiency of stearoyl-CoA desaturase-1 aggravates colitogenic potential of adoptively transferred effector T cells

Abstract

Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially reduced oleate in cell membranes. An altered SCD1 level was observed during intestinal inflammation; however, its role in modulating inflammatory bowel disease remains elusive. Herein, we investigated the colitogenic capacity of Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model. Splenic effector T cells (CD4⁺CD25^-) from age- and sex-matched wild-type (WT) and Scd1KO mice were isolated by FACS and intraperitoneally administered to Rag1KO mice, which were monitored for the development of colitis. At day 60 postcell transfer, Rag1KO mice that received Scd1KO CD4⁺CD25^- T cells displayed accelerated and exacerbated colitis than mice receiving WT CD4⁺CD25^- T cells. Intriguingly, Scd1KO CD4⁺CD25^- T cells display augmented inflammatory cytokine profile and cellular membrane fluidity with a concomitant increase in proinflammatory saturated fatty acids, which we postulate to potentially underlie their augmented colitogenic potential.

Keywords: MUFA; SCD1; colitis; intestinal inflammation; membrane fluidity.