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United States Department of Agriculture

Agricultural Research Service

Research Project: IMPACT OF EARLY DIETARY FACTORS ON CHILD DEVELOPMENT AND HEALTH Title: Inhibition of th17 cells and promotion of tregs in fc gamma chain-deficient mice contributes to the attenuated atherosclerotic lesions

Authors
item Ng, Hongpong -
item Burris, Ramona -
item Nagarajan, Shanmugam -

Submitted to: Journal of Immunology
Publication Type: Abstract Only
Publication Acceptance Date: December 11, 2010
Publication Date: April 1, 2011
Citation: Ng, H., Burris, R., Nagarajan, S. 2011. Inhibition of th17 cells and promotion of tregs in fc gamma chain-deficient mice contributes to the attenuated atherosclerotic lesions [abstract]. Journal of Immunology. 186(1_Meeting Abstract):112.1.

Interpretive Summary: Heart attack is one of the major causes of death in the United States. Heart attack is caused by thickening of blood vessels. This process is called atherosclerosis. Coating blood vessels with bad cholesterol, also known as LDL, causes atherosclerosis. LDL undergoes chemical modification. One of the chemically modified LDL is known as oxidized-LDL. Immune system recognizes oxidized-LDL as a foreign protein. This results in generation of antibody responses. In this study we examined if antibody response contributes to the progression of the disease. We used a genetically modified mouse model. Cells from this mouse do not recognize antibody complex. We showed that atherosclerotic lesions are reduced in this mouse model. We also showed attenuated lesion in this mouse model is due to reduced inflammatory responses. In our future studies we plan to address whether dietary intervention early in life could inhibit the generation of oxLDL and antibody response.

Technical Abstract: The presence of anti-oxLDL IgG is well documented in clinical and animal studies. However, the role for Fc Rs to the progression of atherosclerosis has not been studied in detail. In the present study, we investigated the role for activating Fc R in the progression of atherosclerosis using apoE-Fc -chain double knockout (DKO) mice. Relative to apoE KO mice, arterial lesion formation was significantly decreased in apoE-Fc -chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fc -chain DKO mice. Cytokine responses by activated CD4+ cells showed higher levels of both IL-10 and IFN- secretion. Moreover, compared to apoE KO mice, anti-oxLDL IgG1 (Th2) and IgG2a (Th1) were increased in apoE-Fc gamma-chain DKO mice. Interestingly, the number of Th17 cells and the secretion of IL-17 by activated CD4+ cells were decreased in apoE-Fc -chain DKO mice. Notably, the number of T-regulatory cells, expression of mRNA, and secretion of TGF-beta and IL-10 were increased in apoE-Fc-chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fc gamma-chain DKO mice. Collectively, our data suggest that activating Fc R promotes atherosclerosis by inducing Th17 response in the hyperlipidemic apoE KO mouse model. Our findings indicate that blocking activating Fc R may be a possible therapeutic approach to inhibit T cell responses contributing to the progression of atherosclerosis.

Last Modified: 10/31/2014
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