Pathogenicity control

Distinct subsets of the T_H17 subset of helper T cells have been identified on the basis of their cytokine profiles and pathogenicity. In Cell, Regev and colleagues use single-cell RNA sequencing to profile T_H17 cells isolated from the central nervous system of mice with experimental autoimmune encephalomyelitis or differentiated in vitro in various conditions to identify four previously unknown genes encoding products that control the pathogenic phenotype of T_H17 cells: Gpr65, Plzp, Toso and Cd5l. Kuchroo and colleagues show that CD5L is expressed in non-pathogenic T_H17 cells but not in pathogenic T_H17 cells that infiltrate the central nervous system or were differentiated with IL-23. CD5L deficiency increases the amount of saturated fatty acids and lowers the amount of polyunsaturated fatty acids in T_H17 cells. The former enrich binding of the transcription factor RORγt to the Il17 and Il23r loci, while the latter increase its binding to the Il10 locus. Thus, CD5L regulates the transcriptional activity of RORγt and the cytokine profile of T_H17 cells by controlling the fatty acid composition of the lipidome.

Cell (19 November 2015) doi:10.1016/j.cell.2015.11.009 & doi:10.1016/j.cell.2015.10.068