Abstract
Though the presence of antioxidized low-density lipoprotein IgG is well documented in clinical and animal studies, the role for FcγRs to the progression of atherosclerosis has not been studied in detail. In the current study, we investigated the role for activating FcγR in the progression of atherosclerosis using apolipoprotein E (apoE)-Fcγ-chain double-knockout (DKO) mice. Relative to apoE knockout (KO) mice, arterial lesion formation was significantly decreased in apoE-Fcγ-chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fcγ-chain DKO mice. Compared to apoE KO mice, antioxidized low-density lipoprotein IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-γ secretion by activated T cells was increased in apoE-Fcγ-chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcγ-chain DKO mice is not due to a Th1/Th2 imbalance. Interestingly, the number of Th17 cells and the secretion of IL-17 by activated CD4(+) cells were decreased in apoE-Fcγ-chain DKO mice. Notably, the number of regulatory T cells, expression of mRNA, and secretion of TGF-β and IL-10 were increased in apoE-Fcγ-chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcγ-chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcγ-chain DKO mice was due to reduced IL-6 release by APC of apoE-Fcγ-chain DKO mice. Collectively, our data suggest that activating FcγR promotes atherosclerosis by inducing a Th17 response in the hyperlipidemic apoE KO mouse model.
Highlights
Why The JI? Submit online. Rapid Reviews! 30 days* from submission to initial decision No Triage! Every submission reviewed by practicing scientists Fast Publication! 4 weeks from acceptance to publicatio
To determine the role of activating FcgRs in the progression of atherosclerosis, total activating FcgR deficiency in apolipoprotein E (apoE) KO background was generated
Female apoE-Fcg-chain DKO mice showed a similar reduction in lesions, suggesting there is no effect of gender on the extent of lesions
Summary
We tested the hypothesis that oxLDL-IC binding to activating FcgRs may promote the initiation and progression of atherosclerosis using apoE-Fcg-chain DKO mice by altering CD4+ T cell responses. To investigate if the Th1/Th2 shift could have contributed to the attenuated lesions in the activating FcgR-deficient mice, cytokine response by activated CD4+ T cells (from high fat-fed mice) and anti-oxLDL IgG2a (Th1) and IgG1 (Th2) levels were determined. Quantitative RT-PCR analyses of CD4+ cells showed mRNA expression of IL-10 and IL-4 was ∼3- and 1.5-fold high in apoE-Fcg-chain DKO mice (Fig. 4D).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
