| First Author | Saegusa K | Year | 2002 |
| Journal | J Clin Invest | Volume | 110 |
| Issue | 3 | Pages | 361-9 |
| PubMed ID | 12163455 | Mgi Jnum | J:78331 |
| Mgi Id | MGI:2384231 | Doi | 10.1172/JCI14682 |
| Citation | Saegusa K, et al. (2002) Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. J Clin Invest 110(3):361-9 |
| abstractText | 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 Sjogren 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. |
