Inflammation and Arthritis.

Inflammation is a necessary response to noxic stimuli. If not properly regulated inflammatory responses may become chronic and cause damage. Arthritis is a chronic inflammatory condition. Our research aims at answering the questions: why do some inflammations not resolve and become chronic instead? How can chronic inflammation be ameliorated or resolved?

The innate immune system in arthritis-pathogenesis.

During the early phases of arthritis-pathogenesis regulatory lymphocytes can prevent chronic inflammation (Frey 2010, Win 2016). At later disease stages these cells are much less effective. In current projects we investigate the pathogenetic relevance of myeloid (moncytes/macrophages) and mesenchymal (fibroblasts) cells in arthritis. The aim is to transform the knowledge gained in these projects into novel therapeutic strategies (Wehmeyer 2016).

Neuro-immune interactions in arthritis pathogenesis.

The immune- and nervous system are tightly intertwined. Clinical and experimental evidence suggest an influence of the nervous system on arthritis pathogenesis. We analyzed how neurologially mediated immune-suppression affects arthritis pathogenesis independently of regulatory T cell function (Irmler 2014). Together with our long-term collaboration Partner H.-G. Schaible (Institut für Physiologie, UKJ) we have demonstrated the relevance of IL-17A for arthritis-induced hyperalgesia (Ebbinghaus 2017). In a collaborative research network funded by the Federal Ministry of Education and Research (BMBF) we are currently probing the molecular dialogue between the sympathetic nervous system with synovial fibroblasts and osteoclasts.

Collaboration Partners

Prof. Matthias Gunzer, Institute for Experimental Immunology and Imaging, University Hospital Essen

Prof. Thomas Pap; Institute of Experimental Muscoskeletal Medicine, University Hospital Münster

Prof. Hans-Georg Schaible; Institute of Physiology, Jena University Hospital

Prof. Georg Schett; Department of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen.

10 papers on arthritis

Ebbinghaus, M., G. Natura, G. Segond von Banchet, S. Hensellek, M. Bottcher, B. Hoffmann, F.S. Salah, M. Gajda, T. Kamradt, and H.G. Schaible. 2017.

Interleukin-17A is involved in mechanical hyperalgesia but not in the severity of murine antigen-induced arthritis.

Scientific reports 7:10334.

Wehmeyer, C., S. Frank, D. Beckmann, M. Bottcher, C. Cromme, U. Konig, M. Fennen, A. Held, P. Paruzel, C. Hartmann, A. Stratis, A. Korb-Pap, T. Kamradt, I. Kramer, W. van den Berg, M. Kneissel, T. Pap, and B. Dankbar. 2016.

Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction.

Sci Transl Med 8:330ra335.

Win, S.J., A.A. Kuhl, T. Sparwasser, T. Hunig, and T. Kamradt. 2016.

In vivo activation of Treg cells with a CD28 superagonist prevents and ameliorates chronic destructive arthritis in mice.

European journal of immunology 46:1193-1202.

Llop-Guevara, A., M. Porras, C. Cendon, I. Di Ceglie, F. Siracusa, F. Madarena, V. Rinotas, L. Gomez, P.L. van Lent, E. Douni, H.D. Chang, T. Kamradt, and J. Roman. 2015.

Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice.

Arthritis research & therapy 17:356.

Irmler, I.M., M. Gajda, and T. Kamradt. 2014.

Amelioration of experimental arthritis by stroke-induced immunosuppression is independent of Treg cell function.

Annals of the rheumatic diseases 73:2183-2191.

Kamradt, T., and S. Drube. 2013.

A complicated liaison: IL-33 and IL-33R in arthritis pathogenesis.

Arthritis research & therapy 15:115.

Frey, O., L. Bruns, L. Morawietz, K. Dunussi-Joannopoulos, and T. Kamradt. 2011.

B cell depletion reduces the number of autoreactive T helper cells and prevents glucose-6-phosphate isomerase-induced arthritis.

PLoS One 6:e24718.

Zaiss, M.M., M. Kurowska-Stolarska, C. Bohm, R. Gary, C. Scholtysek, B. Stolarski, J. Reilly, S. Kerr, N.L. Millar, T. Kamradt, I.B. McInnes, P.G. Fallon, J.P. David, F.Y. Liew, and G. Schett. 2011.

IL-33 shifts the balance from osteoclast to alternatively activated macrophage differentiation and protects from TNF-alpha-mediated bone loss.

J Immunol 186:6097-6105.

Frey, O., A. Reichel, K. Bonhagen, L. Morawietz, U. Rauchhaus, and T. Kamradt. 2010. Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis.

Annals of the rheumatic diseases 69:1511-1518.

Schubert, D., B. Maier, L. Morawietz, V. Krenn, and T. Kamradt. 2004.

Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice.

J Immunol 172:4503-4509.