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.
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 humanCL-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.
Authors: Wu-Shiun Hou; Weijie Li; Gernot Keyszer; Ekkehard Weber; Roger Levy; Michael J Klein; Ellen M Gravallese; Steven R Goldring; Dieter Brömme Journal: Arthritis Rheum Date: 2002-03
Authors: Uta Schurigt; Klaus M Hummel; Peter K Petrow; Mieczyslaw Gajda; Renate Stöckigt; Peter Middel; Jochen Zwerina; Tobias Janik; Ricardo Bernhardt; Susann Schüler; Dieter Scharnweber; Felix Beckmann; Paul Saftig; George Kollias; Georg Schett; Bernd Wiederanders; Rolf Bräuer Journal: Arthritis Rheum Date: 2008-02
Authors: Patrick Hargreaves; Douglas Daoudlarian; Michel Theron; Fabrice A Kolb; Marianne Manchester Young; Bernhard Reis; Andre Tiaden; Bettina Bannert; Diego Kyburz; Tobias Manigold Journal: Arthritis Res Ther Date: 2019-07-18 Impact factor: 5.156
Authors: Caio P Gomes; Danilo E Fernandes; Fernanda Casimiro; Gustavo F da Mata; Michelle T Passos; Patricia Varela; Gianna Mastroianni-Kirsztajn; João Bosco Pesquero Journal: Front Cell Infect Microbiol Date: 2020-12-08 Impact factor: 5.293
Authors: Federico Abascal; André Corvelo; Fernando Cruz; José L Villanueva-Cañas; Anna Vlasova; Marina Marcet-Houben; Begoña Martínez-Cruz; Jade Yu Cheng; Pablo Prieto; Víctor Quesada; Javier Quilez; Gang Li; Francisca García; Miriam Rubio-Camarillo; Leonor Frias; Paolo Ribeca; Salvador Capella-Gutiérrez; José M Rodríguez; Francisco Câmara; Ernesto Lowy; Luca Cozzuto; Ionas Erb; Michael L Tress; Jose L Rodriguez-Ales; Jorge Ruiz-Orera; Ferran Reverter; Mireia Casas-Marce; Laura Soriano; Javier R Arango; Sophia Derdak; Beatriz Galán; Julie Blanc; Marta Gut; Belen Lorente-Galdos; Marta Andrés-Nieto; Carlos López-Otín; Alfonso Valencia; Ivo Gut; José L García; Roderic Guigó; William J Murphy; Aurora Ruiz-Herrera; Tomas Marques-Bonet; Guglielmo Roma; Cedric Notredame; Thomas Mailund; M Mar Albà; Toni Gabaldón; Tyler Alioto; José A Godoy Journal: Genome Biol Date: 2016-12-14 Impact factor: 13.583