Both MHC and non-MHC genes regulate inflammation and T-cell response after traumatic brain injury.
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.
Department of Clinical Neuroscience, Karolinska University Hospital, S171 76 Stockholm, Sweden. faiez.al.nimer@ki.se
Faiez
F
Al Nimer
Amennai Daniel
AD
Beyeen
Rickard
R
Lindblom
Mikael
M
Ström
Shahin
S
Aeinehband
Olle
O
Lidman
Fredrik
F
Piehl
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D008285:Major Histocompatibility Complex / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D004676:Myelin Basic Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D004676:Myelin Basic Protein; D010446:Peptide Fragments; C503720:myelin basic protein 63-88