Dermal lymphatic dilation in a mouse model of alopecia areata

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• 作者：John P. Sundberg^a ; ^b ; ^{john.sundberg@jax.org" class="auth_mail" title="E-mail the corresponding author} ; C. Herbert Pratt^a ; Kathleen A. Silva^a ; Victoria E. Kennedy^a ; Timothy M. Stearns^a ; ¹ ; Beth A. Sundberg^a ; Lloyd E. King^b ; Harm HogenEsch^c
• 关键词：AA ; alopecia areata ; Ccr7 ; chemokine (C-C motif) receptor 7 ; Cxcl11 ; chemokine (C-X-C motif) ligand 12 ; Cxcr4 ; chemokine (X-X-C motif) receptor 4 ; Ece1 and 2 ; endothelin converting enzyme 1 and 2 ; End1 ; endothelin 1 ; Flt1 ; FMS-like tyrosine kinase 1 ; H&E ; hematoxylin and eosin stain ; Kdr ; Kinase insert domain receptor ; also known as vascular endothelial growth factor 2 ; VEGF2 ; LYVE1 ; lymphatic vessel endothelial hyaluronan receptor 1 ; PECAM1 ; platelet/endothelial cell adhesion molecule 1 ; former
• 刊名：Experimental and Molecular Pathology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：100
• 期：2
• 页码：332-336
• 全文大小：1211 K

文摘

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.