title: IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe(-/-) mice.
  
  
  METHODS
  We generated IL-22(-/-)Apoe(-/-) mice and fed them high-fat-diet for 14 weeks to characterize atherosclerosis development.
  
  
  RESULTS
  IL-22(-/-)Apoe(-/-) mice exhibited reduced plaque size both in the aorta (p = 0.0036) and the aortic root compared (p = 0.0012) with Apoe(-/-) controls. Moreover, plaque collagen was reduced in IL-22(-/-)Apoe(-/-) mice (p = 0.02) and this was associated with an increased expression of smooth muscle cell (SMC)-α-actin (p = 0.04) and caldesmon (p = 0.016) in the underlying media. Carotid arteries from IL-22(-/-)Apoe(-/-) mice displayed increased expression of genes associated with a contractile SMC phenotype e.g. α-actin (p = 0.004) and caldesmon (p = 0.03). Arterial SMCs were shown to express the IL-22 receptor and in vitro exposure to IL-22 resulted in a down-regulation of alpha actin and caldesmon gene expression in these cells.
  
  
  CONCLUSIONS
  Our observations demonstrate that IL-22 is involved in plaque formation and suggest that IL-22 released by immune cells is involved in activation of vascular repair by stimulating medial SMC dedifferentiation into a synthetic phenotype. This response contributes to plaque growth by enabling SMC migration into the intima but may also help to stabilize the plaque.
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden. Electronic address: Sara.Rattik@med.lu.se.
authors: Sara
authors: S
authors: Rattik
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Karin
authors: K
authors: Hultman
authors: Department of Experimental Medicine, Skåne University Hospital, Lund University, Sweden.
authors: Uwe
authors: U
authors: Rauch
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Ingrid
authors: I
authors: Söderberg
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Lena
authors: L
authors: Sundius
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Irena
authors: I
authors: Ljungcrantz
authors: Department of Experimental Medicine, Skåne University Hospital, Lund University, Sweden.
authors: Anna
authors: A
authors: Hultgårdh-Nilsson
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Maria
authors: M
authors: Wigren
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Harry
authors: H
authors: Björkbacka
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Gunilla Nordin
authors: GN
authors: Fredrikson
authors: Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden.
authors: Jan
authors: J
authors: Nilsson
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation; D007378:Interleukins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D000097043:Interleukin-22
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D002784:Cholesterol; D007378:Interleukins; D018123:Receptors, Interleukin; D014280:Triglycerides; D000097043:Interleukin-22; C415369:interleukin-22 receptor
keywords: Atherosclerosis; Interleukin-22; Smooth muscle cells; Vascular repair