| First Author | Qu P | Year | 2009 |
| Journal | Am J Pathol | Volume | 174 |
| Issue | 3 | Pages | 944-56 |
| PubMed ID | 19179613 | Mgi Jnum | J:146658 |
| Mgi Id | MGI:3838096 | Doi | 10.2353/ajpath.2009.080562 |
| Citation | Qu P, et al. (2009) Critical roles of lysosomal acid lipase in T cell development and function. Am J Pathol 174(3):944-56 |
| abstractText | Lysosomal acid lipase (LAL) cleaves cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. In LAL gene-knockout (lal(-/-)) mice, blockage of cholesteryl ester and triglyceride metabolism led to abnormal organization of the thymus and spleen, as well as neutral lipid accumulation in these organs. LAL deficiency impaired T cell development in the thymus. Peripheral T cells were reduced dramatically in lal(-/-) mice, due largely to increased apoptosis and decreased proliferation of lal(-/-) T cells in the thymus and peripheral compartments. These lal(-/-) T cells lost the ability to respond to T cell receptor stimulation, including reduced expression of cell surface receptor CD69, abolishment of T cell proliferation, and decreased expression of T lymphokines after stimulation by either anti-CD3 plus anti-CD28 or phorbol-12-myristate-13-acetate and ionomycin. Differentiation of Th1 and Th2 CD4(+) effector lymphocytes by T cell receptor stimulation was blocked in lal(-/-) mice. The ratio of CD4(+)CD25(+)FoxP3(+) Tregs to CD4(+) T cells was increased in lal(-/-) spleens. Bone marrow chimeras demonstrated retardation of T cell development and maturation in lal(-/-) mice due to defects in T cell precursors. Therefore, LAL, its downstream genes, and lipid mediators all play essential roles in development, homeostasis, and function of T cells. The altered development and function of lal(-/-) T cells contributes to disease formation in various organs during LAL deficiency. |
