A1.81 Mincle is not essential in T-cell independent arthritis models
Autor: | Birgit Niederreiter, Josef S Smolen, Marije I. Koenders, Silvia Hayer, Kurt Redlich, Wim B. van den Berg, Tetyana Shvets |
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Rok vydání: | 2014 |
Předmět: |
Pathology
medicine.medical_specialty Innate immune system business.industry T cell Immunology Arthritis Inflammation medicine.disease General Biochemistry Genetics and Molecular Biology Pathogenesis Immune system medicine.anatomical_structure Rheumatology Rheumatoid arthritis medicine Immunology and Allergy Synovial fluid medicine.symptom business |
Zdroj: | Annals of the Rheumatic Diseases. 73:A35.3-A36 |
ISSN: | 1468-2060 0003-4967 |
Popis: | Background C-type lectin receptor Mincle (also known as Clecsf9, Clec4e) is expressed by monocytes, macrophages and dendritic cells and involved in immune response to various infections. Recent reports showed elevated levels of Mincle in synovial fluid and PBMCs from RA patients and a linkage of Mincle polymorphisms to lower susceptibility of RA in humans (GuoJP et al 2011;Wu X. Y et al 2012). Objectives (I) To assess the expression of Mincle in inflamed paws in experimental arthritis. (II) To investigate the role of mincle deficiency in the pathogenesis of inflammatory, erosive arthritis by investigating mincle -/- mice in human tumor necrosis factor transgenic (hTNFtg) arthritis model and the K/BxN serum transfer model. Methods Expression levels of Mincle mRNA was determined in inflamed paws from hTNFtg and IL1 -/- IL6 -/- hTNFtg mice by qPCR. To study the role of mincle deficiency in experimental arthritis, we generated mincle -/- hTNFtg mice as well as their hTNFtg littermates. Mice were weekly assessed for clinical signs of arthritis from week 4 to 11 after birth. We quantitatively analysed inflammatory joint destruction in H&E, TRAP and TB stained sections from hind paws. The effect of mincledeficiency was also evaluated in the K/BxN serum transfer model. Therefore, mincle -/- and mincle +/+ mice received i.v. injections of K/BxN serum on day 1 and day 3. Animals were assessed from day1 to 12 for clinical signs of arthritis. Quantitative histopathological analysis were performed as above mentioned in hind paws. Results We found elevated mRNA expression levels of mincle in paw extracts from hTNFtg mice and reduced levels in IL1 -/- IL6 -/- hTNFtg mice. However, by generating mincle -/- hTNFtg mice, we found no marked difference in clinical course of arthritis compared to their hTNFtg littermates from week 5 to week 11 after birth. Moreover, histological analysis revealed similar extends in synovial inflammation, subchondral bone erosions and cartilage damage indicating that mincle is not essentially involved in the pathogenesis of TNF-mediated inflammatory, erosive arthritis. In addition, the transfer of K/BxN serum into mincle -/- animals revealed no significant difference in clinical signs compared to their mincle +/+ littermates. Likewise, we found no marked difference in the extend of synovial inflammation, bone and cartilage destruction in hind paws between mincle -/- and mincle +/+ animals. Conclusion Lacking of C-type lectin receptor mincle does not modulate the pathogenesis of T-cell independent, innate immunity driven arthritis models indicating that mincle is not essentially involved in innate immune responses in the pathogenesis of rheumatoid arthritis. |
Databáze: | OpenAIRE |
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