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Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Interleukin-27 receptor limits atherosclerosis in Ldlr-/- mice
Ekaterina K Koltsova1, Gisen Kim, Kathleen M Lloyd
1Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ekoltsova@liai.org
Circulation Research
|August 29, 2012
Summary
Interleukin-27 (IL-27) receptor signaling suppresses atherosclerosis by reducing inflammatory cell recruitment. Its absence promotes T-helper 17 responses and chemokine production, worsening arterial disease.
Area of Science:
- Immunology
- Cardiovascular Biology
- Inflammation Research
Background:
- Atherosclerosis is a chronic inflammatory disease.
- The role of anti-inflammatory cytokines, like Interleukin-27 (IL-27), in atherosclerosis is not well understood.
- IL-27 receptor subunit Ebi3 is elevated in human atheromas, but its function is unknown.
Purpose of the Study:
- To investigate the role of IL-27 receptor signaling in immune cells during atherosclerosis development.
- To determine how IL-27 signaling impacts immune cell populations and cytokine production in the context of atherosclerosis.
Main Methods:
- Utilized atherosclerosis-prone Ldlr(-/-) mice transplanted with Il27ra(-/-) bone marrow.
- Mice were fed a Western diet for 16 weeks.
- Analyzed atherosclerotic lesion size, immune cell infiltration (CD45+, CD4+ T cells, CD11b+, CD11c+), and chemokine (CCL2) and cytokine (IL-17A, TNF) expression in the aorta.
Main Results:
- Absence of IL-27 receptor signaling led to significantly larger atherosclerotic lesions in multiple aortic regions.
- Increased accumulation of leukocytes, CD4+ T cells, macrophages, and dendritic cells was observed in the aorta.
- Upregulated IL-17A, tumor necrosis factor (TNF), and CCL2 chemokine expression correlated with augmented disease.
Conclusions:
- IL-27 receptor signaling has an antiatherogenic role, suppressing inflammation.
- Lack of IL-27 signaling promotes T-helper 17 responses and pro-inflammatory cytokine/chemokine production.
- IL-27 signaling curbs the recruitment of inflammatory myeloid cells, thereby reducing atherosclerosis progression.
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