title: IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Polyxeni T
authors: PT
authors: Mantani
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Pontus
authors: P
authors: Dunér
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Eva
authors: E
authors: Bengtsson
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Ragnar
authors: R
authors: Alm
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Irena
authors: I
authors: Ljungcrantz
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Ingrid
authors: I
authors: Söderberg
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Lena
authors: L
authors: Sundius
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Fong
authors: F
authors: To
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Jan
authors: J
authors: Nilsson
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Harry
authors: H
authors: Björkbacka
authors: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden; Faculty of Health and Society, Malmö University, Malmö, Sweden.
authors: Gunilla Nordin
authors: GN
authors: Fredrikson
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001018:Aortic Diseases / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D020381:Interleukin-17 / Q000494:pharmacology / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001057:Apolipoproteins E; D020381:Interleukin-17; D015848:Interleukin-5; C044203:anti-IgM
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