Die Rolle von Toll like receptor 4 in der Pathogenese der Kollagen-induzierten Arthritis
Final Report Abstract
The possible role of TLR4 in inflammatory joint disease, i.e. tolerance breakdown, establishing a Th1 response against collagen Il and destruction of bone and cartilage within the joints was evaluated by inducing disease in BIO, DBA/1 J and B10/DBA/1J-TLR4-/- mice. The effect of the mutation on the course of the disease and its pathology was studied. The TLR4 mutation strongly affected diseases severity and mildly affected disease onset and that was reflected in the histopathological evaluation of joint destructions in IFA induced CIA . However, TLR4 has a dual role with protective effects on adaptive immune function observed in Ips pretreated mice in CFA induced CIA. This disease aggravating effect of TLR4 was also observed in Ipr/lpr mice as compared to wt mice, contradictory to the previous results suggesting that the TLR4 pathway is partially impaired in Fas mutant mice. Based on our studies, TLR4 plays significant roles in arthritis, with an arthritis ameliorating effect in the chronic phases but with arthritis aggravating function before disease onset by suppression of the adaptive immune response. Therefore, targeting TLR4 in arthritis may be a valid option, but the exact timing will require future studies.
Publications
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Fine mapping of collagen-induced arthritis quantitative trait loci in an advanced intercross line. J Immunol. 2006 Nov 15;177(10):7042-9
Yu X, Bauer K, Wernhoff P, Koczan D, Möller S, Thiesen HJ, Ibrahim SM
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Combining global genome and transcriptome approaches to identify the candidate genes of small-effect quantitative trait loci in collagen-induced arthritis. Arthritis Res Ther. 2007;9(1):R3
Yu X, Bauer K, Koczan D, Thiesen HJ, Ibrahim SM
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Herpesvirus entry mediator-lg treatment during immunization aggravates rheumatoid arthritis in the collagen-induced arthritis model. J Immunol. 2009 Mar 1;182(5):3139-45
Pierer M, Schulz A, Rossol M, Kendzia E, Kyburz D, Haentzschel H, Baerwald C, Wagner U
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High resolution mapping of CiaS: a common arthritis quantitative trait loci in different species. J Immunol. 2009 Mar 1;182(5);3016-23
Yu X, Teng H, Marques A, Ashgari F, Ibrahim SM
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The mtDNA nt7778 G/T polymorphism affects autoimmune diseases and reproductive performance in the mouse. Hum Mol Genet. 2009 Sep 16
Yu X, Wester-Rosenlöf L, Gimsa U, Holzhueter SA, Marques A, Jonas L, Bauer K, Kunz M, Nizze H, Tiedge M, Holmdahl R, Ibrahim SM
