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

• Published in: Inflammation research Vol. 61; no. 9; pp. 1021 - 1029
• Main Authors: Schurigt, Uta, Eilenstein, Rene, Gajda, Mieczyslaw, Leipner, Carola, Sevenich, Lisa, Reinheckel, Thomas, Peters, Christoph, Wiederanders, Bernd, Bräuer, Rolf
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01.09.2012; Springer Nature B.V
• Subjects: Allergology; Animals; Antigen presentation; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biomedical and Life Sciences; Biomedicine; Cathepsin L; Cathepsin L - deficiency; Cathepsin L - genetics; Cathepsin L - immunology; cathepsins; Cathepsins - genetics; CD4 antigen; Chloride; Clonal selection; Cysteine Endopeptidases - genetics; Dermatology; Epithelium; Helper cells; Hepatitis C virus; Hypersensitivity, Delayed - immunology; Immunoglobulin G - blood; Immunology; Inflammation; Joint diseases; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurology; Original Research Paper; Pharmacology/Toxicology; Rheumatoid arthritis; Rheumatology; Serum Albumin, Bovine - immunology; T-Lymphocytes, Helper-Inducer - immunology; Thymus; T helper cells; Cathepsin L; Cathepsin V; Antigen-induced arthritis; Rheumatoid arthritis
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-012-0495-x

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.