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- Title
Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity.
- Authors
Saegusa, Kaoru; Ishimaru, Naozumi; Yanagi, Kumiko; Arakaki, Rieko; Ogawa, Kouichi; Saito, Ichiro; Katunuma, Nobuhiko; Hayashi, Yoshio
- Abstract
The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for Sjögren syndrome. Specific inhibitor of cathepsin S (Clik60) in vitro markedly impaired presentation of an organ-specific autoantigen, 120-kDa alpha-fodrin, by interfering with MHC class II-peptide binding. Autoantigen-specific T cell responses were significantly and dose-dependently inhibited by incubation with Clik60, but not with inhibitor s of cathepsin B or L. Clik60 treatment of mouse salivary gland cells selectively inhibited autopeptide-bound class II molecules. Moreover, the treatment with Clik60 in vivo profoundly blocked lymphocytic infiltration into the salivary and lacrimal glands, abrogated a rise in serum autoantibody production, and led to recovery from autoimmune manifestations. Thus, inhibition of cathepsin S in vivo alters autoantigen presentation and development of organ-specific autoimmunity. These data identify selective inhibition of cysteine protease cathepsin S as a potential therapeutic strategy for autoimmune disease processes.
- Publication
The Journal of clinical investigation, 2002, Vol 110, Issue 3, p361
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI14682