Cathepsin S inhibitors as novel immunomodulators.
Cathepsin S is one of the major cysteine proteases, and is expressed in the lysosome of antigen presenting cells; primarily dendritic cells, B-cells and macrophages. Cathepsin S is most well known for its critical function in the proteolytic digestion of the invariant chain chaperone molecules, thus controlling antigen presentation to CD4+ T-cells by major histocompatibility complex (MHC) class II molecules or to NK1.1+ T-cells via CD1 molecules. Cathepsin S also appears to participate in direct processing of exogenous antigens for presentation by MHC class II to CD4+ T-cells, or in cross-presentation by MHC class I molecules to CD8+ T-cells. In addition, although direct evidence is still lacking, in its secreted form cathepsin S is implicated in degradation of the extracellular matrix, which may contribute to the pathology of a number of diseases, including arthritis, atherosclerosis and chronic obstructive pulmonary disease. Therefore, inhibition of cathepsin S is a promising target for the development of novel therapeutics for a variety of indications.
Thurmond
Robin L
RL
Johnson & Johnson Pharmaceutical Research & Development LLC, San Diego, CA 92121, USA. rthurmon@prdus.jnj.com
Sun
Siquan
S
Karlsson
Lars
L
Edwards
James P
JP
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use
D007155:Immunologic Factors; D002403:Cathepsins; C028217:cathepsin S