کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
922550 | 921047 | 2011 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Both MHC and non-MHC genes regulate inflammation and T-cell response after traumatic brain injury Both MHC and non-MHC genes regulate inflammation and T-cell response after traumatic brain injury](/preview/png/922550.png)
Genetic regulation of autoimmune neuroinflammation is a well known phenomenon, but genetic influences on inflammation following traumatic nerve injuries have received little attention. In this study we examined the inflammatory response in a rat traumatic brain injury (TBI) model, with a particular focus on major histocompatibility class II (MHC II) presentation, in two inbred rat strains that have been extensively characterized in experimental autoimmune encephalomyelitis (EAE); DA and PVG. In addition, MHC and Vra4 congenic strains on these backgrounds were studied to give information on MHC and non-MHC gene contribution. Thus, allelic differences in Vra4, harboring the Ciita gene, was found to regulate expression of the invariant chain at the mRNA level, with a much smaller effect exerted by the MHC locus itself. Notably, however, at the protein level the MHC congenic PVG-RT1av1 strain displayed much stronger MHCII+ presentation, as shown both by immunolabeling and flow cytometry, than the PVG strain, dwarfing the effect of Ciita. The PVG-RT1av1 strain had significantly more T-cell influx than both DA and PVG, suggesting regulation both by MHC and non-MHC genes. Finally, in terms of outcome, the EAE susceptible DA strain displayed a significantly smaller resulting lesion volume than the resistant PVG-RT1av1 strain. These results provide additional support for a role of adaptive immune response after neurotrauma and demonstrate that outcome is significantly affected by host genetic factors.
Research highlights
► The Ciita haplotype regulates expression of MHC at the mRNA level after TBI.
► MHC genes regulate expression of MHC at the protein level.
► T-cell influx in the brain is regulated by both MHC and non-MHC genes.
► Outcome as measured by lesion volume is mainly regulated by non-MHC genes.
Journal: Brain, Behavior, and Immunity - Volume 25, Issue 5, July 2011, Pages 981–990