Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment

Objective Cathepsin L (CL) is potentially involved in joint destruction and in antigen presentation in rheumatoid arthritis. In order to define the roles of this protease in arthritis development we analysed the antigen-induced arthritis (AIA) in CL-deficient (CL −/− ) mice. Methods Antigen-induced arthritis was induced in CL −/− and wild-type mice. Complete CL deficiency resulted in an impaired positive selection of conventional CD4 + T helper (Th) cells and finally in a reduced number of Th cells. Thus, we addressed the effect of this phenotype by rescuing CD4 + Th cell numbers by transgenic expression of the human CL-like protease cathepsin V (hCV) in thymic epithelium of CL −/− mice [Tg(K14-hCV);CL −/− ]. The arthritis development was monitored by measuring joint swelling. Joint inflammation and destruction were assessed histopathologically. Results The severity of AIA was decreased in CL −/− mice characterized by reduced swelling, decreased inflammation and destruction, and diminished cellular and humoral immune responsiveness. AIA in Tg(K14-hCV);CL −/− mice was associated with a reconstitution of all parameters by normalization of the ratio of regulatory to conventional T cells. Conclusions Cathepsin L has a significant impact on AIA severity by influencing the selection of Th cell populations in the thymus, but seems not play any significant role in the direct joint destruction.