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  • Article: Alopecia areata possibly induced by autoimmune reaction in a patient with human T-cell lymphotropic virus-1-associated myelopathy.
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    ABSTRACT: A 38-year-old female patient suffered from alopecia areata totalis followed by human T-cell lymphotropic virus-1-associated myelopathy (HAM). These two diseases have recently been considered to be related to cell-mediated autoimmune reactions. Immunohistochemistry revealed accumulation of CXCR3(+) CD8(+) T cells around hair bulbs in alopecic lesions. Furthermore, flow cytometric analysis showed the elevated frequency of CD8(+) human leukocyte antigen DR(+) -activated T cells at the initial time and declined at the hair regrowth phase with HAM. CD4(+) CD25(+) adult T-cell leukemia/lymphoma cells were elevated at hair loss phase and decreased after improvement of hair loss. These results suggest that autoreactive and cytotoxic CD8(+) T cells induce not only alopecia areata but also HAM in ATL patients. This case highlights that the autoimmune reactions may play an important role in the pathogenesis of alopecia areata and HAM.
    The Journal of Dermatology 05/2013; 40(5):399-401. · 1.49 Impact Factor
  • Article: Kallikrein-related peptidase 5 functions in proteolytic processing of profilaggrin in cultured human keratinocytes.
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    ABSTRACT: Filaggrin protein is synthesized in the stratum granulosum of the skin and contributes to the formation of the human skin barrier. Profilaggrin is cleaved by proteolytic enzymes and converted to functional filaggrin, but its processing mechanism remains not fully elucidated. Kallikrein-related peptidase 5 (KLK5) is a major serine protease found in the skin, which is secreted from lamellar granules following its expression in the stratum granulosum and activated in the extracellular space of the stratum corneum. Here, we searched for profilaggrin-processing protease(s) by partial purification of epidermal extracts and found KLK5 as a possible candidate. We used high-performance liquid chromatography coupled with electrospray tandem mass spectrometry to show that KLK5 cleaves profilaggrin. Furthermore, based on proximity ligation assay, immunohistochemistry, and immunoelectron microscopy analysis we reveal that KLK5 and profilaggrin co-localize in the stratum granulosum in human epidermis. KLK5 knockdown in normal cultured human epidermal keratinocytes resulted in higher levels of profilaggrin, indicating that KLK5 potentially functions in profilaggrin cleavage.
    Journal of Biological Chemistry 04/2013; · 4.77 Impact Factor
  • Article: D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells.
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    ABSTRACT: BACKGROUND: Dopamine transduces signals via five subtypes of G protein-coupled receptors. Among these subtypes, the D1 and D5 receptors belong to the D1-like group. Although dopamine is known to mediate immune responses, its involvement in cutaneous immunity remains unclear. OBJECTIVE: The aim of this study is to determine the role of dopamine and its D1-like receptors in cutaneous immune responses. METHODS: By using the D1-like receptor antagonist SCH 23390, we examined the role of D1-like receptors in murine models of Th1-type contact hypersensitivity and Th2-type atopic dermatitis in vivo, and in mast cells and Th2 cell differentiation in vitro. RESULTS: Administration of SCH 23390 did not affect Th1-type contact hypersensitivity but suppressed the immediate-type reaction (ITR) and the late phase reaction (LPR) in the atopic dermatitis model. In addition, SCH 23390-treated mice showed higher IFN-γ and lower IL-4 mRNA levels in the ear skin of challenged mice than did non-treated mice as analyzed by real-time RT PCR. Consistently, the passive cutaneous anaphylaxis reaction was significantly reduced in SCH 23390-treated mice. Moreover, dopamine enhanced mast cell degranulation and Th2 cell differentiation, and both activities were abrogated by SCH 23390. CONCLUSION: These findings suggest that the D1-like receptors mediate immediate and late phase skin reactions by promoting Th2 induction and mast cell degranulation.
    Journal of dermatological science 04/2013; · 3.71 Impact Factor
  • Article: Defective epidermal induction of S100A7/psoriasin associated with low frequencies of skin-infiltrating Th17 cells in dermatophytosis-prone adult T cell leukemia/lymphoma.
    Clinical Immunology 03/2013; 148(1):1-3. · 4.05 Impact Factor
  • Article: Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.
    Toshiharu Fujiyama, Yoshiki Tokura
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    ABSTRACT: Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF.
    The Journal of Dermatology 03/2013; · 1.49 Impact Factor

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