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Abe, K. ; Wechs, S. ; Kalaydjiev, S. ; Franz, T.J. ; Busch, D.H. ; Fuchs, H. ; Soewarto, D. ; Behrendt, H. ; Wagner, S. ; Jakob, T. ; Hrabě de Angelis, M.

Novel lymphocyte-independent mechanisms to initiate inflammatory arthritis via bone marrow-derived cells of Ali18 mutant mice.

Rheumatology 47, 292-300 (2008)
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In a large-scale ENU (N-ethyl-N-nitrosourea) mouse mutagenesis programme, we previously have identified and characterized a novel mutation Ali18 that causes inflammatory arthritis like lesions in peripheral joints. In this study, we analysed the immune system of Ali18 mice to understand mechanisms underlying the spontaneous inflammation. METHODS: Humoral and cellular components of the immune system were phenotyped by ELISA and flow cytometry. The contribution of the immune system for phenotype expression was analysed in disease transfer experiments. The involvement of the adaptive immune system was investigated in Ali18;Rag1 double mutants and the influence of environmental factors was analysed in Ali18 mice reared under germ-free conditions. RESULTS: Bone marrow cells from Ali18 mice were able to transfer the disease phenotype to naïve wild-type recipients suggesting that cellular components of the reconstituted immune system were sufficient to induce arthritis. Ali18 mice revealed abnormal leucocyte populations including lymphocytes and granulocytes, as well as increased plasma IL-5 and IgE levels. Ali18;Rag1 double homozygous mutants, which lack mature lymphocytes, still developed arthritis, suggesting that the phenotype is independent of the adaptive immune system. In addition, the arthritis phenotype appeared to be independent from environmental conditions as demonstrated in mice reared under germ-free conditions. CONCLUSIONS: The Ali18 mutation induces inflammatory arthritis through bone marrow-derived cells. However, non-pro-inflammatory cytokine cascades and mature lymphocyte independent-mechanisms are crucial for initiation and progression of the phenotype. Ali18 mice may thus represent a model to study mechanisms involved in seronegative arthritis induced by cells of the innate immune system.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Psoriatic arthritis; Animal model; Inflammatory arthritis; ENU; Mouse mutant
ISSN (print) / ISBN 0003-4908
e-ISSN 1462-0332
Journal Rheumatology
Quellenangaben Volume: 47, Issue: 3, Pages: 292-300 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Institute of Experimental Genetics (IEG)
Institute for Allergy Research (IAF)
Institute of Epidemiology (EPI)
CCG Environmental Dermatology and Allergology (ILBD-KAU)