Effect of fatty acid synthesis inhibition in IL-17-producing gamma delta T (γδT17) cells upon psoriatic inflammation

γδ T cells represent the primary innate source of IL-17 (γδT17) and are known to play a critical role in autoimmune and inflammatory diseases such as psoriasis. We here reported that psoriatic condition (IL-1b and IL-23) reshaped γδT17 cell metabolic signatures and promoted cytokine expression levels compared to homeostatic condition (IL-7). Acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme of fatty acid synthesis (FAS), directs the fate of IL-17-producing CD4 T cells (Th17) differentiation. However, little is known about the role of ACC1-mediated FAS in their innate IL-17-producer counterpart, γδT17 cells. We further investigated the role of FAS in γδT17 by comparing the effect of pharmacological inhibitor Soraphen A (SorA) on DMSO vehicle under psoriatic conditions (IL-1b and IL-23). Interestingly, ACC inhibition shifts the lipid metabolism in γδT17 cells, which allows them to cope with lipid demand without affecting cellular viability. CD27−γδ T cells were expanded in vitro as previously described (McKenzie et al., 2017). This protocol was adapted to have pure CD27−γδ T cells asγδT17 by sorting out expanded CD27-γδTCR+, γδT17 cells. CD27+ γδ T cells were separated and maintained by 20 ng ml–1 IL-7 as γδIFN culture. Sorted γδT17 cells were expanded for three days by 20 ng ml–1IL-7. Then, the cells were harvested and plated at 1 × 106 cells ml–1 in 96-well U-bottom plates to be stimulated with indicated cytokines (5 ng ml–1murine IL-1β/IL-23) in the presence or absence of 2000 nM Soraphen A for 3 hours.