title: Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis.
abstract: Atopic dermatitis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration in the skin. In order to assess the roles of inflammatory cells in this disease, we analysed the activation status and surface markers of various leucocytes in the IL-4 transgenic mouse model of atopic dermatitis, by flow cytometry, immuofluorescence microscopy, and T cell proliferation assays. The studies were performed with a nontransgenic mouse control and transgenic mice at three disease stages: before disease onset, early skin disease, and late skin disease, so that we can delineate the immunological sequence of events. As the skin disease evolves, the skin draining lymph node cells from IL-4-Tg mice show a spontaneous proliferation and a progressively enhanced proliferative response to stimulants including anti-CD3, Con A, PHA, and Staphylococcus enterotoxins A and B. As the disease evolves, the percent of lymphoid organ T cells expressing activation molecules (CD44 and CD69) and costimulatory molecules (ICOS and PD-1) are progressively increased; the percent and total number of T cells are reduced in an incremental manner in the secondary lymphoid organs while the number of T cells infiltrating the skin increases in an incremental fashion; the total number of dendritic antigen presenting cells, macrophages, and NK cells gradually increases in the lymphoid organs. Collectively, our results suggest that there is a continued and progressive migration of activated inflammatory cells from the secondary lymphoid organs into the skin where they participate in immune responses resulting in the pathology associated with inflammation.
authors.affiliation: Department of Dermatology, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: O
authors.initials: O
authors.lastname: Martinez
authors.forename: P
authors.initials: P
authors.lastname: Venkataramani
authors.forename: S-X
authors.initials: SX
authors.lastname: Lin
authors.forename: B S
authors.initials: BS
authors.lastname: Prabhakar
authors.forename: L S
authors.initials: LS
authors.lastname: Chan
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D049109:Cell Proliferation; D003876:Dermatitis, Atopic / Q000276:immunology*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D061026:Programmed Cell Death 1 Receptor; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018960:Hyaluronan Receptors; D060889:Inducible T-Cell Co-Stimulator Protein; D015847:Interleukin-4; D037181:Lectins, C-Type; D061026:Programmed Cell Death 1 Receptor; D000099192:CD69 Antigens; C556694:Icos protein, mouse; C491383:Pdcd1 protein, mouse