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Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis
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Abstracts / Journal of Dermatological Science 84 (2016) e89–e180
P01-44[O1-34] Decreased expression of ELOVL and ceramide synthase in dermatitis caused by repeated exposure to house-dust mite in NC/Nga mice Hiroyuki Kanoh 1,∗ , Asako Ishitsuka 1 , Etsuko Fujine 1 , Shuhei Matsuhaba 2 , Mitsuhiro Nakamura 3 , Naoki Inagaki 2 , Yoshiko Banno 1 , Mariko Seishima 1 1
Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan 2 Laboratory of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan 3 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan Objective: In stratum corneum, intercellular lipids play an important role in the regulation of skin barrier functions. Ceramide is a major component of the intercellular lipids, and average fatty acid chain length of the ceramides correlates with the barrier function. In atopic dermatitis and psoriasis patients, fatty acid chain length of stratum corneum ceramide is shortened. Ceramide synthase (CerS) and elongase of long-chain fatty acids (ELOVL) are the enzymes involved in the elongation of fatty acids of ceramides. We have recently shown that IFN-␥ but not Th2 cytokines decreases the expression of ELOVL and CerS in cultured human keratinocytes. In the present study, we have aimed to evaluate expression of ELOVL and CerS in dermatitis caused by repeated house-dust mite exposure. Methods: A fecal extract of Dermatophagoides farinae was applied to the auricles of NC/Nga mice two times per week for a total of five times. Expression of cytokines and enzymes was determined by quantitative reverse-transcriptase-PCR. Results: Repeated application of house-dust mite extract caused scaling, erythema and thickening of auricles and increases in the expression of IFN-␥, IL-4, IL-12 B, and TNF-␣. Serum total IgE level was also increased. Among seven isozymes of ELOVL, ELOVL4, ELOVL5 and ELOVL6 were predominantly expressed in NC/Nga mice, and the expression levels of ELOVL5 and ELOVL6 were decreased. As for CerS, CerS2, CerS4, CerS5 and CerS6 among six isozymes were predominantly expressed, and the expression levels of CerS4 and CerS5 were decreased. Conclusion: In mice model of dermatitis caused by repeated application of mite antigen, the expression of enzymes involved in the elongation of fatty acids of ceramides was suppressed probably through the action of IFN-␥. http://dx.doi.org/10.1016/j.jdermsci.2016.08.313 P01-45[O1-35] Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis Kanako Matsuyama 1,∗ , Yoko Mizutani 1 , En Shu 1 , Hiroyuki Kanoh 1 , Tatsuhiko Miyazaki 2 , Mariko Seishima 1 1 The Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan 2 The Division of Pathology, Gifu University Hospital, Japan
Background: Porokeratosis is clinically characterized by annular lesions and histologically by the presence of a cornoid lamella (CL) in the epidermis. However, the developing mechanism of
porokeratosis is still unclear. Recently, a pivotal role of Langerhans cells and regulatory T cells in the development of inflammatory dermal lesions has been reported. Objectives: To evaluate the presence and numbers of Langerhans cells and FOXP3+ T cells in porokeratosis lesions. Methods: We performed immunohistochemistry for CD1a, Ki67, CD3, CD4, CD8, FOXP3, and RANKL (receptor activator of nuclear factor B ligand) on samples from 17 porokeratosis lesions and analysed the difference in staining patterns among the CL, the inside of the CL (IC), and the outside of the CL (OC). Results: The numbers of CD1a+ Langerhans cells in the epidermis were significantly decreased, and the numbers of CD1a+ dermal dendritic cells were significantly increased in the CL and IC compared to those in the OC. In addition, there was also an increase in FOXP3-positive cells in the CL but not in the IC and the OC. The expression of RANKL was observed in the suprabasal keratinocytes around the CL. Conclusion: Our findings suggest that the numbers of Langerhans cells are downregulated in the epidermis and the numbers of regulatory T cells and dendritic cells are increased in the CL in the dermis. This immunological alteration may play a key role in the pathogenesis of porokeratosis. http://dx.doi.org/10.1016/j.jdermsci.2016.08.314 P01-46[O1-36] Autoantibody profile and clinical manifestations related to anti-synthetase syndrome Hiroko Fukamatsu 1,∗ , Yoji Hirai 1 , Tomoko Miyake 1 , Tatsuya Kaji 1 , Toshihisa Hamada 1 , Seiichiro Norikane 2 , Keiji Iwatsuki 1 1
Department of Dermatology, Okayama University Hospital, Japan 2 Department of Radiology, Okayama University Hospital, Japan Several anti-aminoacyl-tRNA synthetase (ARS) antibodies (Abs) have been detected in patients with dermatomyositis (DM). In order to understand clinical manifestations related to antisynthetase syndrome (ASS), we screened 24 sera obtained from 24 patients with DM or related disorders, using an ELISA kit coated with 5 different ARS antigens: Jo-1, PL-7, PL-12, EJ, and KS, compared to 20 control sera. All the positive sera were further examined to identify the each targeted antigen, using ELISA plates coated with one of the 5 ARSs. All sera were also examined for TIF1-␥, MDA5 and Mi-2. Seven of 24 samples were positive for anti-ARS Abs (ARS group). Of the 7 sera, 3 were reactive with Jo-1, 1 with PL-7, 1 with PL-12, 1 with EJ, and 1 with KS. No overlap or cross-reactivity was found against the ARS antigens. In the remaining 17 sera negative for anti-ARS Abs (non-ARS group), the sera were positive for TIF1␥ in 5, for MDA5 in 4, and for Mi-2 in 1, while no positive sera were found in the ARS group. No clear difference was observed in cutaneous manifestations including mechanic’s hands between 2 groups. In the ARS group, the occurrence of fever and interstitial lung disease (ILD) were observed in 5 (71%) and 7 (100%), respectively, the incidences of which were significantly high as compared with those in the non-ARS group (12% and 29%, respectively). As for the pattern of ILD, a fibrotic NSIP pattern was observed in 5 of 7 patients in the ARS group. The time until 50% reduction of serum KL-6 levels reached promptly in the ARS group (99 ± 31 days) as compared with the non-ARS group (196 ± 62 days). Patients with ASS may possess one of anti-ARS Abs in a mutual exclusion fashion,
Abstracts / Journal of Dermatological Science 84 (2016) e89–e180
P01-44[O1-34] Decreased expression of ELOVL and ceramide synthase in dermatitis caused by repeated exposure to house-dust mite in NC/Nga mice Hiroyuki Kanoh 1,∗ , Asako Ishitsuka 1 , Etsuko Fujine 1 , Shuhei Matsuhaba 2 , Mitsuhiro Nakamura 3 , Naoki Inagaki 2 , Yoshiko Banno 1 , Mariko Seishima 1 1
Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan 2 Laboratory of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan 3 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan Objective: In stratum corneum, intercellular lipids play an important role in the regulation of skin barrier functions. Ceramide is a major component of the intercellular lipids, and average fatty acid chain length of the ceramides correlates with the barrier function. In atopic dermatitis and psoriasis patients, fatty acid chain length of stratum corneum ceramide is shortened. Ceramide synthase (CerS) and elongase of long-chain fatty acids (ELOVL) are the enzymes involved in the elongation of fatty acids of ceramides. We have recently shown that IFN-␥ but not Th2 cytokines decreases the expression of ELOVL and CerS in cultured human keratinocytes. In the present study, we have aimed to evaluate expression of ELOVL and CerS in dermatitis caused by repeated house-dust mite exposure. Methods: A fecal extract of Dermatophagoides farinae was applied to the auricles of NC/Nga mice two times per week for a total of five times. Expression of cytokines and enzymes was determined by quantitative reverse-transcriptase-PCR. Results: Repeated application of house-dust mite extract caused scaling, erythema and thickening of auricles and increases in the expression of IFN-␥, IL-4, IL-12 B, and TNF-␣. Serum total IgE level was also increased. Among seven isozymes of ELOVL, ELOVL4, ELOVL5 and ELOVL6 were predominantly expressed in NC/Nga mice, and the expression levels of ELOVL5 and ELOVL6 were decreased. As for CerS, CerS2, CerS4, CerS5 and CerS6 among six isozymes were predominantly expressed, and the expression levels of CerS4 and CerS5 were decreased. Conclusion: In mice model of dermatitis caused by repeated application of mite antigen, the expression of enzymes involved in the elongation of fatty acids of ceramides was suppressed probably through the action of IFN-␥. http://dx.doi.org/10.1016/j.jdermsci.2016.08.313 P01-45[O1-35] Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis Kanako Matsuyama 1,∗ , Yoko Mizutani 1 , En Shu 1 , Hiroyuki Kanoh 1 , Tatsuhiko Miyazaki 2 , Mariko Seishima 1 1 The Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan 2 The Division of Pathology, Gifu University Hospital, Japan
Background: Porokeratosis is clinically characterized by annular lesions and histologically by the presence of a cornoid lamella (CL) in the epidermis. However, the developing mechanism of
porokeratosis is still unclear. Recently, a pivotal role of Langerhans cells and regulatory T cells in the development of inflammatory dermal lesions has been reported. Objectives: To evaluate the presence and numbers of Langerhans cells and FOXP3+ T cells in porokeratosis lesions. Methods: We performed immunohistochemistry for CD1a, Ki67, CD3, CD4, CD8, FOXP3, and RANKL (receptor activator of nuclear factor B ligand) on samples from 17 porokeratosis lesions and analysed the difference in staining patterns among the CL, the inside of the CL (IC), and the outside of the CL (OC). Results: The numbers of CD1a+ Langerhans cells in the epidermis were significantly decreased, and the numbers of CD1a+ dermal dendritic cells were significantly increased in the CL and IC compared to those in the OC. In addition, there was also an increase in FOXP3-positive cells in the CL but not in the IC and the OC. The expression of RANKL was observed in the suprabasal keratinocytes around the CL. Conclusion: Our findings suggest that the numbers of Langerhans cells are downregulated in the epidermis and the numbers of regulatory T cells and dendritic cells are increased in the CL in the dermis. This immunological alteration may play a key role in the pathogenesis of porokeratosis. http://dx.doi.org/10.1016/j.jdermsci.2016.08.314 P01-46[O1-36] Autoantibody profile and clinical manifestations related to anti-synthetase syndrome Hiroko Fukamatsu 1,∗ , Yoji Hirai 1 , Tomoko Miyake 1 , Tatsuya Kaji 1 , Toshihisa Hamada 1 , Seiichiro Norikane 2 , Keiji Iwatsuki 1 1
Department of Dermatology, Okayama University Hospital, Japan 2 Department of Radiology, Okayama University Hospital, Japan Several anti-aminoacyl-tRNA synthetase (ARS) antibodies (Abs) have been detected in patients with dermatomyositis (DM). In order to understand clinical manifestations related to antisynthetase syndrome (ASS), we screened 24 sera obtained from 24 patients with DM or related disorders, using an ELISA kit coated with 5 different ARS antigens: Jo-1, PL-7, PL-12, EJ, and KS, compared to 20 control sera. All the positive sera were further examined to identify the each targeted antigen, using ELISA plates coated with one of the 5 ARSs. All sera were also examined for TIF1-␥, MDA5 and Mi-2. Seven of 24 samples were positive for anti-ARS Abs (ARS group). Of the 7 sera, 3 were reactive with Jo-1, 1 with PL-7, 1 with PL-12, 1 with EJ, and 1 with KS. No overlap or cross-reactivity was found against the ARS antigens. In the remaining 17 sera negative for anti-ARS Abs (non-ARS group), the sera were positive for TIF1␥ in 5, for MDA5 in 4, and for Mi-2 in 1, while no positive sera were found in the ARS group. No clear difference was observed in cutaneous manifestations including mechanic’s hands between 2 groups. In the ARS group, the occurrence of fever and interstitial lung disease (ILD) were observed in 5 (71%) and 7 (100%), respectively, the incidences of which were significantly high as compared with those in the non-ARS group (12% and 29%, respectively). As for the pattern of ILD, a fibrotic NSIP pattern was observed in 5 of 7 patients in the ARS group. The time until 50% reduction of serum KL-6 levels reached promptly in the ARS group (99 ± 31 days) as compared with the non-ARS group (196 ± 62 days). Patients with ASS may possess one of anti-ARS Abs in a mutual exclusion fashion,