An epigenetic mechanism for decreased MHC II expression in macrophages under simulated microgravity

摘要

Mechanisms of microgravity-caused immunosuppression are not fully elucidated. In the present study, the effects of simulated microgravity upon the expression of CD80 (Cluster of differentiation 80), CD86 (Cluster of differentiation 86), and MHC II (Major histocompatibility complex class II molecules) on macrophage cells were investigated. Primary mouse macrophages were cultured under normal gravity and simulated microgravity, respectively. The expression of those molecules was examined. The expression of I-A~b(an MHC class II molecule), but not of CD80 or CD86, on non-stimulated murine macrophages was decreased by simulated microgravity. Furthermore, the induction of CD86 expression by LPS (Lipopolysaccharide) and the induction of I-A~b expression by IL-4 (Interleukin 4) on macrophages were inhibited by simulated microgravity. Molecular mechanisms underlying the decreased MHC II expression on macrophages under simulated microgravity were studied. Decreased expression of the master regulatory factor of MHC II (the class II transactivator) and decreased histone acetylation were found in those cells. Increasing histone acetylation through inhibition of histone deacetylases was able to increase the expression of I-A~b in macrophages under simulated microgravity. This indicates that the decreased histone acetylation in macrophages under simulated microgravity contributed, at least partly, to the decreased expression of I-A~b in these cells. This study therefore revealed an epigenetic mechanism for decreased MHC II expression in macrophages under simulated microgravity.