Phosphoinositide acyl chain saturation drives CD8+ effector T cell signaling and function

The ATP-exporting channel Pannexin-1 promotes CD8+T cell effector and memory responses

“…6n). Additionally, oleic acid, a PI biosynthesis-forming medium-chain fatty acid 54 , had decreased intracellular levels in Panx1-KO CD8 + T cells (Extended Data Fig. 5j).…”

“…5h), among the few other candidates found was Hydroxylauric Acid, a medium-chain fatty acid 53 . Medium-chain fatty acids are used by CD8 + T cells for fatty acid biosynthesis, a fundamental step in effector CD8 + T cell activation 54 . Intracellular phospholipid biosynthesis metabolites were sharply decreased in Panx1-KO effector-like CD8 + T cells (Fig.…”

“…6l). PIs compose the immunological synapse 55 , and saturated (i.e., with less than 2 double bonds) phosphatidylinositol phosphates (PIPs) compose lipid rafts found during late activation, to sustain effector function 54 . Panx1-KO effector-like CD8 + T cells had specific defects in saturated PIs (Fig.…”

“…5l). Saturated PI biosynthesis leads to activation of the MAP-kinase (MAPK) signaling pathway to sustain CD8 + T cell activation and effector function 54 . RNA expression of some MAPK pathway genes is decreased in Panx1-KO effector-like CD8 + T cells (Fig.…”

“…A secondary antibody (Alexa Fluor 647 anti-rabbit IgG) was used for detection of pACC. Alexa Fluor 488-conjugated Cholera Toxin B was used for detection of lipid rafts and stained as described in 54 . Flow cytometric analyses were performed on FACS Symphony or LSR Fortessa (BD Biosciences) and data was analyzed using FlowJo software (Treestar).…”