Artikel
Autoantibodies targeting CXCR3 and CXCR4 affect the expression of their cognate receptors in lung tissue of the ApoE knockout mouse model
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Veröffentlicht: | 8. Oktober 2019 |
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Gliederung
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Background: Autoantibodies recognising different G Protein-coupled receptors (GPCR) are found in rheumatic diseases such as systemic sclerosis (SSc) and healthy people, forming specific regulatory networks. In particular, high amounts of anti-CXCR3 autoantibodies seem to be protective, while low amounts are associated with deterioration of lung function.
Methods: Immunoglobulin G (IgG) containing different amounts of anti-GPCR autoantibodies derived from SSc patients and healthy donors (HD) were passively transferred into ApoE-Knockout (KO) mice. Mice were fed a western type diet (WTD). Following sacrifice, mRNA and protein expression of CXCR3, CXCR4 and Angiotensin II type 1 receptor (AT1R) were examined in lung tissue via quantitative real-time polymerase chain reaction and immunohistochemistry. Besides, murine anti-GPCR autoantibodies were determined by ELISA and the atherosclerotic plaque size in the aorta was measured by red oil staining.
Results: Passive transfer of IgG, derived from SSc and containing low amounts of human anti-CXCR3 antibodies (SSc-IgG), into ApoE KO mice induced a decreased CXCR3 mRNA expression in the lung compared to HD-IgG (p<0.05). In contrast, the lower the CXCR3 mRNA expression in the lung of mice treated with SSc-IgG, the higher the amount of murine anti-CXCR3 autoantibodies (rs= -0.65, p=0.07). Additionally, a high CXCR3 mRNA expression in the lung of control mice went along with high amounts of murine anti-CXCR4 autoantibodies (rs= 0.76, p<0.05). However, despite the presence of numerous CXCR3+ and CXCR4+ cells, no differences in protein expression were observed between HD-IgG- and SSC-IgG-treated or control mice. Of note, high amounts of murine anti-CXCR4 autoantibodies in control as well as HD-IgG-treated mice were accompanied by a decreased size of atherosclerotic plaques in the aorta (rs=-0.8571 or -0.8929, respectively, p<0.05).
Conclusion: Both human and murine anti-CXCR3 and anti-CXCR4 autoantibodies might modulate the expression of their cognate GPCR in the lung of the ApoE KO mouse model. Due to a lack of differences in terms of protein expression, it may be necessary to examine individual cell types.