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Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis

Engelbertsen, Daniel LU ; Foks, Amanda C. ; Alberts-Grill, Noah ; Kuperwaser, Felicia ; Chen, Tao ; Lederer, James A. ; Jarolim, Petr ; Grabie, Nir and Lichtman, Andrew H. (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
publishing date
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 Hagerstown, MD
external identifiers
  • scopus:84948074237
  • pmid:26494229
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
2020-07-08 05:00:28
@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},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {2526--2535},
  publisher    = {Lippincott Williams  Wilkins Hagerstown, MD},
  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},
}