title: Resistance to alopecia areata in C3H/HeJ mice is associated with increased expression of regulatory cytokines and a failure to recruit CD4+ and CD8+ cells.
abstract: Grafting alopecia areata affected C3H/HeJ mouse skin to littermates induces alopecia areata, but high dietary soy oil reduces alopecia areata susceptibility. Alopecia areata affected and resistant mice were characterized to evaluate possible mechanisms involved in alopecia areata resistance. Of 44 mice that received alopecia areata affected skin grafts but failed to develop alopecia areata, only two of 22 receiving further alopecia areata affected skin grafts developed alopecia areata, whereas 39 of 44 controls developed alopecia areata. Alopecia areata affected skin contained increased numbers of CD4+ and CD8+ cells, increases in pro inflammatory T helper 1 and T helper 2 type cytokines, and upregulation of CD28, CD40L, and their ligands. In draining lymph nodes, a relatively high number of antigen-presenting cells was recovered, whereas several CD44v variants were downregulated. In contrast, alopecia areata resistant mouse skin did not display increased numbers of CD4+ and CD8+ cells, whereas counter-regulatory cytokines interleukins 4 and 10 were upregulated. High expression of CD28, CD80, CD86, CD40, CTLA4, CD44v variants, and FasL occurred in alopecia areata resistant mouse spleens. In vitro, lymph node cells of susceptible and resistant mice responded equally to a mitogenic stimulus, but only lymph node cells from alopecia areata affected mice displayed an increased response with T cell receptor stimulation via anti-CD3 cross-linking. These results suggest alopecia areata is a cell-mediated autoimmune disease, but alopecia areata affected skin graft hosts may resist alopecia areata onset through active counter-regulatory mechanisms. Because alopecia areata resistant mice showed unimpaired responsiveness and a transient inflammatory response towards the graft, it is suggested that alopecia areata develops as a consequence of an inappropriate immune response regulation.
authors.affiliation: Department of Dermatology, Philipp University, Marburg, Germany; The Jackson Laboratory, Bar Harbor, ME, USA. kevin@keratin.com
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McElwee
authors.forename: Rolf
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Pia
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: Elke
authors.initials: E
authors.lastname: Wenzel
authors.forename: Sabina
authors.initials: S
authors.lastname: Kissling
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
mesh_terms: D000506:Alopecia Areata / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D012867:Skin / Q000166:cytology / Q000276:immunology; D016038:Skin Transplantation
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins