TY - JOUR
T1 - Myeloid interferon-γ receptor deficiency does not affect atherosclerosis in LDLR-/- mice
AU - Boshuizen, Marieke C.S.
AU - Neele, Annette E.
AU - Gijbels, Marion J.J.
AU - van der Velden, Saskia
AU - Hoeksema, Marten A.
AU - Forman, Ruth A.
AU - Muller, Werner
AU - Van den Bossche, Jan
AU - de Winther, Menno P.J.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Background and aims: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNγ) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell-specific targeting of IFNγ or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNγ targets, we here addressed the involvement of myeloid IFNγ signaling in murine atherosclerosis. Methods: Bone marrow was isolated from interferon gamma receptor 2 chain (IFNγR2) wildtype and myeloid IFNγR2 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 IFNγ signaling attenuated the myeloid IFNγ response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNγR2 deficiency could be observed. Conclusion: Overall, our data argue against a role for myeloid IFNγR2 in atherosclerosis development. Since myeloid IFNγ signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNγ acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets.
AB - Background and aims: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNγ) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell-specific targeting of IFNγ or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNγ targets, we here addressed the involvement of myeloid IFNγ signaling in murine atherosclerosis. Methods: Bone marrow was isolated from interferon gamma receptor 2 chain (IFNγR2) wildtype and myeloid IFNγR2 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 IFNγ signaling attenuated the myeloid IFNγ response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNγR2 deficiency could be observed. Conclusion: Overall, our data argue against a role for myeloid IFNγR2 in atherosclerosis development. Since myeloid IFNγ signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNγ acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets.
KW - Atherosclerosis
KW - Interferon gamma receptor
KW - Macrophage
KW - Mouse model
UR - http://www.scopus.com/inward/record.url?scp=84956639796&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.atherosclerosis.2016.01.026
DO - https://doi.org/10.1016/j.atherosclerosis.2016.01.026
M3 - Article
C2 - 26828750
SN - 0021-9150
VL - 246
SP - 325
EP - 333
JO - Atherosclerosis
JF - Atherosclerosis
ER -