IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.
IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any...
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doaj-3ea2bfd76251400c9387235ccc16e3822020-11-25T02:01:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011725510.1371/journal.pone.0117255IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.Polyxeni T MantaniPontus DunérEva BengtssonRagnar AlmIrena LjungcrantzIngrid SöderbergLena SundiusFong ToJan NilssonHarry BjörkbackaGunilla Nordin FredriksonIL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apo)E deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC) natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.http://europepmc.org/articles/PMC4309452?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Polyxeni T Mantani Pontus Dunér Eva Bengtsson Ragnar Alm Irena Ljungcrantz Ingrid Söderberg Lena Sundius Fong To Jan Nilsson Harry Björkbacka Gunilla Nordin Fredrikson |
spellingShingle |
Polyxeni T Mantani Pontus Dunér Eva Bengtsson Ragnar Alm Irena Ljungcrantz Ingrid Söderberg Lena Sundius Fong To Jan Nilsson Harry Björkbacka Gunilla Nordin Fredrikson IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. PLoS ONE |
author_facet |
Polyxeni T Mantani Pontus Dunér Eva Bengtsson Ragnar Alm Irena Ljungcrantz Ingrid Söderberg Lena Sundius Fong To Jan Nilsson Harry Björkbacka Gunilla Nordin Fredrikson |
author_sort |
Polyxeni T Mantani |
title |
IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. |
title_short |
IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. |
title_full |
IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. |
title_fullStr |
IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. |
title_full_unstemmed |
IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. |
title_sort |
il-25 inhibits atherosclerosis development in apolipoprotein e deficient mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apo)E deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC) natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses. |
url |
http://europepmc.org/articles/PMC4309452?pdf=render |
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