Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis
(2015) In Arteriosclerosis, Thrombosis, and Vascular Biology 35(12). p.2526-2535- Abstract
Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results-We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr-/-rag1-/- mice. To investigate the role of ILCs in atherosclerosis, ldlr-/-rag1-/- mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that... (More)
Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results-We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr-/-rag1-/- mice. To investigate the role of ILCs in atherosclerosis, ldlr-/-rag1-/- mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that expand CD25+ ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2-treated mice. These IL-2-treated mice had reduced very low-density lipoprotein cholesterol and increased triglycerides compared with controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila, and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2 complex-induced eosinophilia but did not change lesion size. Conclusions-This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in very low-density lipoprotein cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis.
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- author
- Engelbertsen, Daniel LU ; Foks, Amanda C. ; Alberts-Grill, Noah ; Kuperwaser, Felicia ; Chen, Tao ; Lederer, James A. ; Jarolim, Petr ; Grabie, Nir and Lichtman, Andrew H.
- publishing date
- 2015-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Atherosclerosis, cytokines, eosinophils, interleukin, triglycerides
- in
- Arteriosclerosis, Thrombosis, and Vascular Biology
- volume
- 35
- issue
- 12
- pages
- 10 pages
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:26494229
- scopus:84948074237
- ISSN
- 1079-5642
- DOI
- 10.1161/ATVBAHA.115.306048
- language
- English
- LU publication?
- no
- id
- 8cccad48-2d3a-488a-8d02-183ef9e1dd64
- date added to LUP
- 2019-07-22 09:49:37
- date last changed
- 2024-01-16 09:03:01
@article{8cccad48-2d3a-488a-8d02-183ef9e1dd64,
abstract = {{<p>Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results-We demonstrate that CD25<sup>+</sup> ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr<sup>-/-</sup>rag1<sup>-/-</sup> mice. To investigate the role of ILCs in atherosclerosis, ldlr<sup>-/-</sup>rag1<sup>-/-</sup> mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that expand CD25<sup>+</sup> ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2-treated mice. These IL-2-treated mice had reduced very low-density lipoprotein cholesterol and increased triglycerides compared with controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila, and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2 complex-induced eosinophilia but did not change lesion size. Conclusions-This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in very low-density lipoprotein cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis.</p>}},
author = {{Engelbertsen, Daniel and Foks, Amanda C. and Alberts-Grill, Noah and Kuperwaser, Felicia and Chen, Tao and Lederer, James A. and Jarolim, Petr and Grabie, Nir and Lichtman, Andrew H.}},
issn = {{1079-5642}},
keywords = {{Atherosclerosis; cytokines; eosinophils; interleukin; triglycerides}},
language = {{eng}},
month = {{12}},
number = {{12}},
pages = {{2526--2535}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
title = {{Expansion of CD25<sup>+</sup> Innate Lymphoid Cells Reduces Atherosclerosis}},
url = {{http://dx.doi.org/10.1161/ATVBAHA.115.306048}},
doi = {{10.1161/ATVBAHA.115.306048}},
volume = {{35}},
year = {{2015}},
}