Dendritic Cell Subsets in the Skin and Their Functional Role in Contact Hypersensitivity

Objectives: Skin is a primary epithelial organ, which protects our body from the surrounding environment. Besides physical barrier machineries, skin also contains a number of immune components that actively participate in the protective immune responses. Dendritic cells (DCs) are professional antigen-presenting cells and they are essentially required for mediating innate and adaptive immunity. Although emerging studies have demonstrated distinct resident DC subsets in the skin, their subset-specific functions still need to be elucidated. Methods: We reviewed recent works on the DC subset discrimination and specification in the mouse skin. To understand the DC subset-dependent functional diversity, we especially focused on the murine contact hypersensitivity (CHS), an experimental model of human allergic contact dermatitis. Furthermore, we discussed our recent work on the role of epidermal Langerhans cells (LCs) in CHS. Results: Murine skin harbors at least three DC subsets: (i) epidermal LCs, (ii) Langerin+ dermal DCs and (iii) Langerin- dermal DCs. Using more sophisticated cell markers, recent study has described monocyte-derived DCs in the skin. The role of each DC subset in CHS was somewhat inconsistent and redundant from study to study and needs further elaborative works for the general acceptance. Conclusion: Continuous efforts to understand the functional diversity among each cutaneous DC subset will be needed to develop the new anti-inflammatory and anti-tumor strategies by targeting relevant skin DC population in vivo

Circuit Structure and Control Method to Reduce Size and Harmonic Distortion of Interleaved Dual Buck Inverter

A new circuit structure and control method for a high power interleaved dual-buck inverter are proposed. The proposed inverter consists of six switches, four diodes and two inductors, uses a dual-buck structure to eliminate zero-cross distortion, and operates in an interleaved mode to reduce the current stress of switch. To reduce the total harmonic distortion at low output power, the inverter is controlled using discontinuous-current-mode control combined with continuous-current-mode control. The experimental inverter had a power-conversion efficiency of 98.5% at output power = 1300 W and 98.3% at output power = 2 kW, when the inverter was operated at an input voltage of 400 V-DC, output voltage of 220 V-AC/60 Hz, and switching frequency of 20 kHz. The total harmonic distortion was < 0.66%, which demonstrates that the inverter is suitable for high-power dc-ac power conversion.11Ysciescopu

Regulation of Expression of B7 by Murine Langerhans Cells: A Direct Relationship Between B7 mRNA Levels and the Level of Surface Expression of B7 by Langerhans Cells

Cultured BALB/c epidermal Langerhans cells express high levels of the costimulatory molecule B7 on their surfaces relative to levels expressed on fresh Langerhans cells. Quantitation of relative amounts of B7 mRNA in fresh epidermal cells and cultured epidermal cells following amplification of mRNA signals via reverse transcriptase – polymerase chain reaction, hybridization of PCR products with radiolabeled internal oligonucleotide probes, resolution of hybrids in non-denaturing polyacrylamide gels, and detection by autoradiography revealed dramatically (approximately one thousandfold) higher levels of B7 mRNA in cultured epidermal cells (10-40% 1-A+) as compared with fresh epidermal cells (1 – 4% I-A+). Levels of B7 mRNA in cultured epidermal cells were also substantially greater than those detected in a reference B lymphoma cell line (CH-1). Analysis of 87 mRNA expression in subpopulations of cultured epidermal cells demonstrated that essentially all of the B7 mRNA was present in Langerhans cells; cells bearing I-A and CD45 antigens. Cultured keratinocytes did not contain appreciable amounts of B7 mRNA. These results are consistent with previous data regarding surface expression of 87 by cLC and also demonstrate that fLC are essentially devoid of B7 mRNA and surface protein

Metastasis of Transitional Cell Carcinoma to the Lower Abdominal Wall 20 Years after Cystectomy

Iatrogenic implantation has been the main cause in the majority of cases of transitional call carcinoma (TCC) with metastasis to the abdominal wall. A 66-year-old woman had undergone radical cystectomy 20 years prior to presenting. Radiological investigations revealed one mass in the left lower abdominal wall and one mass in the right inguinal area. She underwent wide excision of the lesions that revealed metastasis of TCC. This report describes this case of a woman with bladder carcinoma who developed a metastasis in the anterior abdominal wall following an apparent disease-free interval of 20 years

Therapeutic Mode of Action of Methotrexate

Objectives: Methotrexate (MTX) has been used in clinical practice for over a half-century and its action mechanism is believed to rely on the direct inhibition of DNA synthesis leading to suppression of cell proliferation. However, its anti-inflammatory action mechanism is not fully explained. In some autoimmune or overactive immune-related diseases such as psoriasis, it has been demonstrated that interleukin (IL)-23/IL-17/lL-22 pathway plays a key role in disease pathogenesis. In this study, we aimed to investigate the suppressive action of MTX on the IL[1]23/1 L-17/1 L-22 pathway in psoriasis. Methods: We made a model of psoriasis on mice using imiquimod (IMQ). The mice were divided into three groups: disease-free control group and disease-induced groups with no treatment and MTX-treatment. Clinical, histological and immunological parameters were evaluated among the groups. Results: Treatment with MTX decreased the psoriatic skin changes and the histological alterations induced by IMQ. MTX exerted its treatment effects via inhibition of the main players in the pathogenetic axis, the IL-23, IL-17A, F and IL-22, that were found to be increased in the diseased mice. Regulatory T cells expressing CTLA4 or GITR or PD1 molecules on their surface were not related to these decrements. Conclusion: The therapeutic action mechanism of MTX is related to the direct inhibition of the IL-23/1 L-17/1 L-22 pathway, but not the induction of inhibitory molecules or expansion of regulatory T cells

Transition from Pemphigus Foliaceus to Pemphigus Vulgaris: Case Report with Literature Review

The transition between the main subtypes of pemphigus, pemphigus vulgaris (PV), and pemphigus foliaceus (PF) has rarely been reported. Moreover, the development of PV in a patient with PF is much more unusual than that of PF in a patient with PV. We report a 48-year-old man who presented with cutaneous lesions showing the typical clinical and histological features of PF. Five years later, his skin lesions became extensive and he developed oral erosions. His condition did not respond well to steroids and azathioprine. Histological examination of a vesicle disclosed suprabasal acantholysis in contrast to the subcorneal acantholysis discovered upon initial histological evaluation. Indirect immunofluorescence revealed IgG antikeratinocyte cell surface antibodies at a titer of 1:640. The titer was 1:160 at initial diagnosis. Upon immunoblotting, the patient's serum reacted with 130 kiloDalton (kDa) and 160 kDa proteins, suggesting desmoglein (Dsg) 3 and 1, respectively. We herein report an unusual case of PV that developed from PF during the disease's flare-up

Combined Treatment of an Intratumoral Injection of Dendritic Cells and Systemic Chemotherapy (Paclitaxel) for Murine Fibrosarcoma

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma

Immunotherapy of Malignant Melanoma with Tumor Lysate-Pulsed Autologous Monocyte-Derived Dendritic Cells

PURPOSE: Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea. MATERIALS AND METHODS: Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time. RESULTS: Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients. CONCLUSION: In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.ope