Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production

Abstract

We have previously established a correlation between reduced mitochondrial glycerol-3-phosphate acyltransferase-1 (GPAT-1) activity and decreased proliferation in splenic T-lymphocytes from aged rats. To better understand the immunoregulatory role of GPAT-1, we examined T-lymphocyte function in young GPAT-1 knockout (KO) mice. We show that without GPAT-1, T-lymphocyte proliferation is inhibited and activation induced apoptosis is increased. Th-1 (IL-2 and IFN-γ) cytokine secretion is reduced, and Th-2 (IL-4 and IL-10) cytokine secretion is increased. These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species. Furthermore, we show increased arachidonate content and subsequent increased prostaglandin E2secretion, which may inhibit T-lymphocyte proliferation. Taken together, we show a novel link between GPAT-1 and changes in T-lymphocyte function. These data have broad health implications because GPAT-1 suppression has recently been implicated as a new target for preventing insulin sensitivity and hepatic steatosis and we show that immune function may also be affected. Interestingly, the changes in young GPAT-1 KO splenic T-lymphocytes are similar to defects commonly seen in T-lymphocytes from aged rodents, which further underscores the significance of GPAT-1 in T-lymphocyte function.