Effector CD4+CD25- T cells from Stearoyl CoA Desaturase deficient mice drive chronic colitis in RAG-1KO mice (MUC5P.761)

Abstract

Abstract Fatty acids in lipid bilayer substantially influence membrane fluidity and thus dictate cellular functions. Stearoyl CoA Desaturase (SCD-1) is a lipogenic enzyme that assists in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayer. Accordingly SCD-1KO mice display substantially reduced oleate in cell membranes. We investigated the colitogenic capacity of effector T-cells from SCD-1KO mice and their WT littermates in adoptive T-cell transfer colitis model. Splenic effector T-cells (CD4+CD25-) from age and gender matched WT and SCD-1KO mice were isolated by cell sorting using magnetic beads and flow cytometry. RAG-1KO (n=5) were administered 5.0x105 CD4+CD25- cells/mouse intraperitoneally and monitored for body weights and colitis development. RAG-1KO mice which received CD4+CD25- cells from SCD-1KO mice displayed colomegaly, splenomegaly, elevated colonic, systemic lipocalin-2, a general inflammatory marker and hallmarks of colitis at histologic level. Interestingly, colonic TNFα and IL-10 gene transcripts were significantly reduced in SCD-1KO CD4+CD25- recipients whereas the opposite is true for iNOS and lipocalin-2. Further, systemic sIL-1Ra was significantly reduced in SCD-1KO CD4+CD25- recipients when compared to WT T cell recipients. Our results demonstrate that effector T-cells from oleate poor environment attain colitogenic properties and may be associated with increased immunoreactivity to gut microbiotal antigens.