TNF-alpha receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice.
Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic pro-inflammatory cytokine with potentially neurodestructive effects and plays a pivotal role in autoimmune demyelinating disease. To address the role of TNF-alpha in the pathogenesis of experimental autoimmune neuritis (EAN), the current study investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN induced by P0 protein peptide 106-125 in TNF-alpha receptor 1 deficient (TNFR1(-/-)) mice. The antigen-presenting capacity of SCs was assessed by the expression of MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as by induction of T cell proliferation in co-cultures of P0 protein peptide 106-125 specific T cells with activated SCs. In addition, the expression of inducible nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry. TNFR1(-/-) EAN mice developed significantly delayed and reduced clinical signs of EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80 and iNOS on SCs were decreased in TNFR1(-/-) mice compared to wild type mice. Likewise, proliferation of P0 protein peptide 106-125 specific T cells simulated by activated SCs of TNFR1(-/-) EAN mice was lower than that of wild type EAN mice. Our data suggest that TNF-alpha may exert pro-inflammatory effects in EAN via TNFR1 by up-regulating the antigen-presenting function and iNOS production of SCs.
Mao
Xi-Jing
XJ
Department of Neurology, First Hospital of Jilin University, Changchun, China.
Zhang
Xing-Mei
XM
Zhang
Hong-Liang
HL
Quezada
Hernan Concha
HC
Mix
Eilhard
E
Yang
Xin
X
Winblad
Bengt
B
Adem
Abdu
A
Zhu
Jie
J
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000201:enzymology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000941:Antigens; D018993:Myelin P0 Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II