title: Dermal lymphatic dilation in a mouse model of alopecia areata.
abstract: Mouse models of various types of inflammatory skin disease are often accompanied by increased dermal angiogenesis. The C3H/HeJ inbred strain spontaneously develops alopecia areata (AA), a cell mediated autoimmune disorder that can be controllably expanded using full thickness skin grafts to young unaffected mice. This provides a reproducible and progressive model for AA in which the vascularization of the skin can be examined. Mice receiving skin grafts from AA or normal mice were evaluated at 5, 10, 15, and 20 weeks after engraftment. Lymphatics are often overlooked as they are small slit-like structures above the hair follicle that resemble artifact-like separation of collagen bundles with some fixatives. Lymphatics are easily detected using lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) by immunohistochemistry to label their endothelial cells. Using LYVE1, there were no changes in distribution or numbers of lymphatics although they were more prominent (dilated) in the mice with AA. Lyve1 transcripts were not significantly upregulated except at 10 weeks after skin grafting when clinical signs of AA first become apparent. Other genes involved with vascular growth and dilation or movement of immune cells were dysregulated, mostly upregulated. These findings emphasize aspects of AA not commonly considered and provide potential targets for therapeutic intervention.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA; Division of Dermatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA. Electronic address: john.sundberg@jax.org.
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: C Herbert
authors.initials: CH
authors.lastname: Pratt
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Silva
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Kennedy
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Stearns
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Sundberg
authors.affiliation: Division of Dermatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: King
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
authors.forename: Harm
authors.initials: H
authors.lastname: HogenEsch
mesh_terms: D000506:Alopecia Areata / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008208:Lymphatic System / Q000378:metabolism / Q000473:pathology*; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins; D008809:Mice, Inbred C3H; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016038:Skin Transplantation / Q000379:methods; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D026901:Membrane Transport Proteins; C492273:LYVE1 protein, mouse
keywords: Autoimmune disease; Inflammation; LYVE1; Lymphatics; PECAM1; SMA