Cathepsin S holds up autoimmunity

Cathepsins are lysosomal cysteine proteases — originally thought to be only non-specific scavengers — that interfere with MHC class II molecules on antigen-presenting cells, but their role autoimmune disease has been unclear. In August 1 Journal of Clinical Investigation, Kaoru Saegusa and colleagues from Tokushima University School of Dentistry, Tokushima, Japan, show that inhibition of cathepsin S in vivo alters autoantigen presentation and prevents development of organ-specific autoimmunity (J Clin Invest 2002, 110:361-369).

Saegusa et al. studied a murine model of Sjögren syndrome (an autoimmune connective tissue disease involving the lacrimal and salivary glands) and observed that in vitro a specific inhibitor of cathepsin S (Clik60) markedly impaired presentation of an organ-specific autoantigen by interfering with MHC class II–peptide binding. In addition, treatment with Clik60 in vivo profoundly blocked lymphocytic infiltration into the salivary and lacrimal glands, abrogated a rise in serum autoantibody production and led...