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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 

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Presentation on theme: "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 "— Presentation transcript:

1 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  Kevin J. McElwee, Rolf Hoffmann, Pia Freyschmidt-Paul, Elke Wenzel, Sabina Kissling  Journal of Investigative Dermatology  Volume 119, Issue 6, Pages (December 2002) DOI: /j x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Immunohistologic appearance of normal, AA-affected, and AA-resistant mouse skin. Normal C3H/HeJ mouse skin is virtually devoid of CD8+ cells (a) as is AA resistant skin (c), but CD8+ cells are present in significant numbers in both perifollicular and intrafollicular locations in AA-affected skin (b). Skin containing anagen stage hair follicles from normal-haired, nonsurgically manipulated mice contain isolated CD4+ cells (d), whereas AA-affected hair follicles exhibit a moderate perifollicular increase in CD4+ cell numbers (e). Mice with failed AA induction after two consecutive skin grafts have skin containing CD4+ cells in numbers similar to that observed for normal mice (f). Isolated macrophages are present in normal-haired skin (g) and variably present in AA-affected skin with some anagen hair follicles the focus of particularly intense macrophage activity (h). AA-resistant mouse skin also contained perifollicular infiltrates (i). Normal-haired skin contained individual dendritic cells (j), whereas AA-affected skin revealed various degrees of dendritic cell infiltration (k) and AA-resistant mouse skin revealed a modest infiltration (l). MHC class I expression was generally absent from normal-haired and AA-resistant skin (m,o), whereas AA-affected skin exhibited intense MHC class I expression in the ORS of some hair follicles that were the focus for intense inflammatory cell activity (n). Similarly, MHC class II expression was absent in the lower dermis of normal-haired and AA-resistant mice except for isolated cells, likely to be dendritic cells (p,r), but AA-affected hair follicles and inflammatory infiltrates highly expressed MHC class II (q). Bar (a–q) = 100 μm. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Flow cytometric analysis of skin-derived cells. A significant increase in CD4+, CD8+, and sIgM+ cells in AA-affected skin contrasted with significant increases in macrophages and dendritic cells for mice with failed AA after one or two consecutive grafts (a). Whereas AA-affected mice demonstrated increased expression in all cytokines evaluated, mice with resistance to AA had significant increases in cytokines IL-4 and IL-10 but no increase in proinflammatory cytokines, IL-6 and IL-12 (b). AA-affected mice exhibited significant increases in costimulation molecules CD28, CD40, CD80, and CD86 (c) and increased expression of CD44v6 (d). The mean ±SD of 10–20 analyses are given. Filled shapes indicate significant increased or decreased frequency of expression (p< 0.01) in surgically manipulated mice vs normal-haired mice, open shapes indicate no significant difference. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Flow cytometric analysis of lymph node derived cells. Mice with AA had a high percentage of macrophages and dendritic cells present in draining lymph nodes (a) and high expression of antigen-presenting cell associated cytokine IL-6 (b). Limited changes in cell surface molecule expression was apparent (c), but AA-affected mice demonstrated reduced cellular expression of migratory associated molecules pan CD44, CD44v3, CD44v7, and CD44v10 (d). The mean±SD of 10–20 analyses are given. Filled shapes indicate significant increased or decreased frequency of expression (p< 0.01) in surgically manipulated mice vs normal-haired mice, open shapes indicate no significant difference. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Flow cytometric analysis of spleen-derived cells. Mice resistant to AA development revealed significant increases in macrophages and dendritic cells and a modest increase in sIgM+ cells in the spleen (a). Limited changes in cytokine expression were observed (b), but increased expression of CD28, CD80, CD86, and CD40 in AA-resistant mice directly contrasted with depressed expression of the CD25, CD28, CD40L, and CD80 in AA-affected mice (c). A direct contrast in increased expression of CD44v7 in AA-resistant mice compared with depression in AA-affected mice was also observed (d). The mean±SD of 10–20 analyses are given. Filled shapes indicate significant increased or decreased frequency of expression (p< 0.01) in surgically manipulated mice vs normal-haired mice, open shapes indicate no significant difference. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions


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