Citation

Al Nimer F, Beyeen AD, Lindblom R, Ström M, Aeinehband S, Lidman O, Piehl F. Brain Behav. Immun. 2011; 25(5): 981-990.

Affiliation

Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska University Hospital, S171 76 Stockholm, Sweden.

Copyright

(Copyright © 2011, Elsevier Publishing)

DOI

10.1016/j.bbi.2010.10.017

PMID

20974248

Abstract

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-RT1(av1) 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-RT1(av1) 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-RT1(av1) 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.

Language: en