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

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Abstract

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.

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Acknowledgments

The authors are grateful for technical assistance to Uta Griechen, Cornelia Hüttich, Waltraud Seul, and Renate Stöckigt. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Interdisziplinäres Zentrum für klinische Forschung (IZKF) Jena (to BW and RB).

Conflict of interest

None.

Ethics Approval

Animal studies were approved by the Thuringian governmental committee for animal protection.

Author information

Author notes

  1. Uta Schurigt

    Present address: Institute for Molecular Infection Biology, University of Würzburg, Josef-Schneider-Str. 2/D15, 97080, Würzburg, Germany

Authors and Affiliations

  1. Institute of Pathology, University Hospital, Friedrich Schiller University, Jena, Germany

    Uta Schurigt, Rene Eilenstein, Mieczyslaw Gajda & Rolf Bräuer

  2. Animal Facility, University Hospital, Friedrich Schiller University, Jena, Germany

    Carola Leipner

  3. Institute of Molecular Medicine and Cell Research, Albert Ludwigs University, Freiburg, Germany

    Lisa Sevenich, Thomas Reinheckel & Christoph Peters

  4. BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University, Freiburg, Germany

    Thomas Reinheckel & Christoph Peters

  5. Institute of Biochemistry I, University Hospital, Friedrich Schiller University, Jena, Germany

    Bernd Wiederanders

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  1. Uta Schurigt
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Correspondence to Uta Schurigt.

Additional information

Responsible Editor: John Di Battista.

B. Wiederanders and R. Bräuer shared senior authorship.

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Schurigt, U., Eilenstein, R., Gajda, M. et al. Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment. Inflamm. Res. 61, 1021–1029 (2012). https://doi.org/10.1007/s00011-012-0495-x

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  • DOI: https://doi.org/10.1007/s00011-012-0495-x

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