The Distinctive Immunologic Pathogenesis Differentiates Atopic Comorbidity Status in Prurigo Nodularis / 대한피부과학회지

Background@#Prurigo nodularis (PN) is a chronic pruritic skin disorder with a large number of hyperkeratotic nodules. The precise mechanisms of its pathogenesis remain unknown. PN has been linked to atopic dermatitis (AD), but its association remains unclear. @*Objective@#We aimed to investigate the clinical, histological, and immunohistochemical characteristics of patients with PN and PN underlying AD (PN-AD). @*Methods@#Eight patients were recruited for PN, PN-AD, and eight normal subjects, respectively. Skin tissues were obtained from patients and healthy subjects for histological and immunohistochemical analyses. @*Results@#Histological examination showed increased epidermal thickness and dermal inflammatory cell counts in the PN-AD and PN groups compared to normal subjects. Immunohistochemical analyses revealed that the expression of interleukin (IL)-4, IL-13, IL-18, IL-31, IL-33, interferon (IFN)-γ, stromal-derived factor (SDF) 1-α and thymic stromal lymphopoietin (TSLP) was increased in the tissues of PN-AD and PN groups, in which the staining intensities of IL-4, IL-13, SDF1-α and TSLP in the PN-AD group were higher than those in the PN group, but the differences were not statistically significant. Conversely, the staining intensities of IL-18, IL-33 and IFN-γ were significantly higher in the PN group than those in the PN-AD group. @*Conclusion@#The pathogenesis of PN may differ from that of PN-AD, in which IL-18, IL-33 and IFN-γ may be associated, implying that epidermal injury is the initial cause of IL-18 and IL-33 induction, which then increases IFN-γ, resulting in the inflammatory process of PN.

Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis

PURPOSE: Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. METHODS: ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. RESULTS: We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4+ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. CONCLUSIONS: These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.

Upregulation of CD47 in Regulatory T Cells in Atopic Dermatitis

PURPOSE: Regulatory T (Treg) cells are key modulators in the immune system. Recent studies have shown that atopic dermatitis (AD) patients have higher numbers of Treg cells; however, little is known about the specific phenotype and function of Treg cells in AD. MATERIALS AND METHODS: To identify differentially expressed proteins in peripheral induced Treg cells in AD and naturally derived Treg cells in normal controls, CD4?CD25? Treg cells were isolated from thymus tissue of normal mice and the spleens of AD mice. Membrane proteins were extracted, and quantitative proteomics labeling with Tandem Mass Tags (TMT) was performed, followed by one-dimensional liquid chromatography/tandem mass spectrometry analysis. RESULTS: Using TMT labeling, we identified 510 proteins, including 63 membrane proteins and 16 plasma membrane proteins. CD47 was one of the upregulated proteins in Treg cells in AD spleens. Although CD47 was expressed in all CD4? and CD8? T cells, a significantly higher expression of CD47 was observed in the Treg cells of AD mice and AD patients than in those of normal mice and healthy controls. Furthermore, Treg cells from the spleen showed a significantly higher expression of CD47 than those from the thymus. CONCLUSION: We found that CD47 is highly expressed in the Treg cells of AD mice, particularly in the spleen. Based on our results, we propose that CD47(high) Treg cells are likely induced Treg cells and that upregulated CD47 in the Treg cells of AD patients may play a role in the increased population of Treg cells in AD.

Upregulation of CD47 in Regulatory T Cells in Atopic Dermatitis

PURPOSE: Regulatory T (Treg) cells are key modulators in the immune system. Recent studies have shown that atopic dermatitis (AD) patients have higher numbers of Treg cells; however, little is known about the specific phenotype and function of Treg cells in AD. MATERIALS AND METHODS: To identify differentially expressed proteins in peripheral induced Treg cells in AD and naturally derived Treg cells in normal controls, CD4?CD25? Treg cells were isolated from thymus tissue of normal mice and the spleens of AD mice. Membrane proteins were extracted, and quantitative proteomics labeling with Tandem Mass Tags (TMT) was performed, followed by one-dimensional liquid chromatography/tandem mass spectrometry analysis. RESULTS: Using TMT labeling, we identified 510 proteins, including 63 membrane proteins and 16 plasma membrane proteins. CD47 was one of the upregulated proteins in Treg cells in AD spleens. Although CD47 was expressed in all CD4? and CD8? T cells, a significantly higher expression of CD47 was observed in the Treg cells of AD mice and AD patients than in those of normal mice and healthy controls. Furthermore, Treg cells from the spleen showed a significantly higher expression of CD47 than those from the thymus. CONCLUSION: We found that CD47 is highly expressed in the Treg cells of AD mice, particularly in the spleen. Based on our results, we propose that CD47(high) Treg cells are likely induced Treg cells and that upregulated CD47 in the Treg cells of AD patients may play a role in the increased population of Treg cells in AD.