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

First Author  Collison LW Year  2008
Journal  Am J Physiol Cell Physiol Volume  295
Issue  6 Pages  C1543-9
PubMed ID  18971390 Mgi Jnum  J:143259
Mgi Id  MGI:3826295 Doi  10.1152/ajpcell.00371.2007
Citation  Collison LW, et al. (2008) Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production. Am J Physiol Cell Physiol 295(6):C1543-9
abstractText  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-gamma) 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 E(2) secretion, 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.
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