Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset of EAE though impairment of toll-like receptor 3 cascade

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Ryo OkadaHiroshi Nakanishi

Abstract

The objective of this study is to investigate the role of cathepsin H (CatH), a lysosomal cysteine protease, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in CatH-deficient mice (CatH-/-) and wild-type littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35-55. The effects of CatH deficiency were determined by clinical scoring, mRNA expression levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-β (IFN-β) by splenocytes. CatH-/- showed a significantly earlier disease onset of EAE and increased Th1 cell differentiation in splenocytes. Splenocytes prepared from immunized CatH-/- showed a significant decrease in poly(I:C)-induced increased TLR3 expression, interferon regulatory factor 3 (IRF3) phospholylation and IFN-β secretion. Therefore, CatH deficiency impaired TLR3-mediated activation of IRF3 and consequent secretion of IFN-β from dendritic cells, leading to the enhancement of Th1 cell differentiation and consequent early disease onset of EAE.

References

Apr 1, 1995·Journal of Leukocyte Biology·W P LafuseB S Zwilling
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tarik TouilBruno Gran
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alejandra Garcia-CattaneoPhilippe Benaroch
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Jun 16, 2015·PloS One·Euan Ramsay Orr Allan, Robin Michael Yates

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