Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice.

Background: Ketoprofen (KP) is widely used as a topical nonsteroidal anti-inflammatory drug that inhibits prostaglandin (PG) biosynthesis. As PGE(2) upregulates the antigen-presenting activity of Langerhans cells (LCs), i.e.

Possible pathogenic role of Th17 cells for atopic dermatitis.

The critical role of IL-17 has recently been reported in a variety of conditions. Since IL-17 deeply participates in the pathogenesis of psoriasis and keratinocyte production of certain cytokines, the involvement of T helper cell 17 (Th17) in atopic dermatitis (AD) is an issue to be elucidated. To evaluate the participation of Th17 cells in AD, we successfully detected circulating lymphocytes intracellularly positive for IL-17 by flow cytometry, and the IL-17+ cell population was found exclusively in CD3+CD4+ T cells.

"Nagashima-type" keratosis as a novel entity in the palmoplantar keratoderma category.

Background: "Nagashima-type" keratosis is characterized by transgressive and nonprogressive palmoplantar keratoderma (PPK) with an autosomal recessive trait. Because its clinical manifestations are similar to but milder than those of mal de Meleda, it was originally described as a mild form of Meleda-type PPK. Since then, about 20 cases have been reported in the Japanese-language literature.

Alterations of serum Th1 and Th2 chemokines by combination therapy of interferon-gamma and narrowband UVB in patients with mycosis fungoides.

Background: Mycosis fungoides (MF) is a T cell neoplasm with elevation of serum Th2 chemokines. Although interferon-gamma (IFN-gamma) administration and narrowband-UVB (NB-UVB) phototherapy are used for the treatment of MF, a combination therapy of these two modalities is not fully established.

Objectives: To define whether the combination of IFN-gamma and NB-UVB affects the balance of serum levels of Th1 and Th2 chemokines in patients with MF.

Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines.

There are immediate, late-phase, and delayed-type reactions to exogenous agents. In IFN-gamma-knockout (IFN-gamma(-/-)) and wild-type B6 mice, we examined the response to picryl chloride (PCl) for assessing delayed-type reactions, and the responses to repeatedly challenged FITC for immediate and late-phase reactions. The delayed-type hypersensitivity was depressed in IFN-gamma(-/-) mice, and the immediate and late-phase reactions were enhanced in IFN-gamma(-/-) mice.

Percutaneous penetration via hand eczema is the major accelerating factor for systemic absorption of toluene and xylene during car spray painting.

Background: For absorption of organic solvents, the respiratory tract is well known as the major site, but percutaneous absorption might be critical in some workplaces.

Objectives: The aim of the study is to determine whether the skin, if disordered, is 1 of the major routes of organic solvent absorption.

Patients/methods: 72 male workers who painted the car body in the booth of a Japanese car company were participated in this study.

Epidermal chemokines and modulation by antihistamines, antibiotics and antifungals.

Growing evidence has demonstrated that chemokines released from epidermal cells control inflammatory skin diseases. Keratinocytes elaborate both Th1- and Th2-associated chemokines, although the former is more abundantly produced than the latter. Downmodulation of keratinocyte production of chemokines is one of the therapeutic approaches for cutaneous inflammatory disorders.

Primary cutaneous anaplastic large cell lymphoma with fatal leukemic outcome in association with CLA and CCR4-negative conversion.

A 70-year-old Japanese male presented with a 1-year history of skin tumors, which were diagnosed as primary cutaneous anaplastic large cell lymphoma (ALCL) because of the CD3(low+), CD4(+), CD25(+), CD30(+), CD45RO(+), CD71(+), HLA-DR(+), CD8(-), CD56(-), and NPM/ALK(-) phenotype and monoclonal T-cell receptor-rearranged property of tumor cells as well as the absence of systemic involvement. At this time, the tumor cell was positive for cutaneous lymphocyte-associated antigen (CLA) and TH(2) chemokine receptor CCR4. The eruption had repeatedly appeared and spontaneously regressed or regressed by virtue of several therapeutic modalities, including radiotherapy, interferon-alpha and chemotherapy, until the tumor cell invaded the gastric mucosa and spread to the peripheral blood 5 years later.

Adult T-cell leukemia/lymphoma cells from blood and skin tumors express cytotoxic T lymphocyte-associated antigen-4 and Foxp3 but lack suppressor activity toward autologous CD8+ T cells.

Adult T cell leukemia/lymphoma (ATL) cells share the CD4(+)CD25(+) phenotype with regulatory T (Treg) cells. However, it is still controversial whether ATL cells are Treg cells. The aim of the present study was to investigate the Treg nature of ATL cells obtained from peripheral blood and skin tumors in terms of their phenotype and function.

Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1.

Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1-4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1-/- mice.

CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells.

CCR7 is regarded as an essential chemokine receptor for cutaneous dendritic cell (DC) migration into the regional lymph nodes. However, complete migratory inhibition cannot be obtained in CCR7-deficient mice, suggesting that there exist other chemokine receptors involved in this process. Initially, we found that CXCR4 was highly expressed on migrated cutaneous DCs and that its ligand, CXCL12, was detected in the LYVE-1(+) lymphatic vessels in the skin.

Augmented expression of programmed death-1 in both neoplastic and non-neoplastic CD4+ T-cells in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a CD4(+)CD25(+) T-cell malignancy infected with human T-cell leukemia virus type-I (HTLV-I). HTLV-I infection causes the T-cell dysfunction, which contributes to the immunodeficient state of the patients. Programmed death-1 (PD-1) can negatively regulate T-cell response, when its ligand, PD-L1 or PD-L2 mainly expressed on antigen presenting cells, binds to this B7 family receptor.