Myeloid interferon-gamma receptor deficiency does not affect atherosclerosis in LDLR(-/-) mice.


BACKGROUND AND AIMS: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNgamma) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell-specific targeting of IFNgamma or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNgamma targets, we here addressed the involvement of myeloid IFNgamma signaling in murine atherosclerosis. METHODS: Bone marrow was isolated from interferon gamma receptor 2 chain (IFNgammaR2) wildtype and myeloid IFNgammaR2 deficient mice and injected into lethally irradiated LDLR(-/-) mice. After recovery mice were put on a high fat diet for 10 weeks after which atherosclerotic lesion analysis was performed. In addition, the accompanying liver inflammation was assessed. RESULTS: Even though absence of myeloid IFNgamma signaling attenuated the myeloid IFNgamma response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNgammaR2 deficiency could be observed. CONCLUSION: Overall, our data argue against a role for myeloid IFNgammaR2 in atherosclerosis development. Since myeloid IFNgamma signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNgamma acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets.