The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Maj... more The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Major advances in our understanding of the autonomic and sensory transmission and function include the recognition of the phenotypic expression of a variety of transmitters and modulators that often coexist in individual neurons, the concept of co-transmission and chemical coding, the evidence for local effector functions of primary afferent nerves, and the discovery of plasticity of both the autonomic and the sensory nervous system during development, aging, diseases states, and inflammation. Co-transmission or plurichemical transmission, which indicates the release of more than one chemical messenger from the same neuron, enables autonomic and sensory neurons to exert a fine and highly regulated control of various functions such as circulation and immune response. The concept of chemical coding, in which the combination of transmitters/modulators is established, allows the identification of functional classes of neurons with their projections and targets. In addition to transmitters and modulators, autonomic and sensory neurons express multiple receptors, including G-proteincoupled and ion-gated receptors, further supporting the complexity of autonomic and sensory transmission and function. Autonomic neurons regulate the internal environment and maintain multiple homeostatic functions, and sensory neurons act as receptive structures that activate their targets in response to stimulation but also exert effector functions including the control of blood flow and vascular permeability, maintenance of mineralized tissue, and regulation of gene expression.
Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates an... more Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates and articular cartilage and has a key role in the biophysical and biomechanical properties of cartilage. Recently, heterozygous mutations in the ACAN gene, which encodes aggrecan, have been identified in patients with short stature and accelerated bone age. We herein report another family with a heterozygous ACAN mutation associated with idiopathic short stature along with accelerated bone age and early-onset herniation of the lumbar discs at the levels of L1/2 through L5/S1. Whole-exome sequencing identified a novel heterozygous frameshift mutation in the ACAN gene (c.1744delT; p.Phe582fs*69) in all of the affected family members but not in the unaffected one, providing further evidence that ACAN haploinsufficiency causes short stature with advanced bone maturation. In addition, we advocate early-onset multiple disc herniation as a novel phenotype associated with ACAN haploinsufficiency.
Spontaneous remission occurs in up to 80% of patients with limited patchy alopecia areata (AA) wi... more Spontaneous remission occurs in up to 80% of patients with limited patchy alopecia areata (AA) within 1 year. Therefore, not all patients of AA simplex/multiplex need extensive treatments, and "wait and see" is one of the choices for some patients. However, once the hair loss show progressive course, it is really difficult to manage well and may be recalcitrant to any treatment in some cases. Hair loss symptom is not life-threatening but severely decreases quality of life. There have been two widely known guidelines for AA from the British Association of Dermatologists and the National Alopecia Areata Foundation (USA). These guidelines have been substantial and provide clues for dermatologists but needed to be updated. Recently, the Japanese Dermatological Association also published a guideline for the management of AA. This guideline suggests treatments followed by recommendations and evidence levels. Several new treatments are added such as corticosteroid pulse therapy a...
1 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the genitalia. Arch Dermatol 1979; 115: 30... more 1 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the genitalia. Arch Dermatol 1979; 115: 306–308. 2 Patterson JW, Kao GF, Graham JH, Helwig EB. Bowenoid papulosis. A clinicopathologic study with ultrastructural observations. Cancer 1986; 57: 823–836. 3 Sweidan NA, Salman SM, Zaynoun ST, Sanaknaki BA, Kibbi AG. Linear bowenoid papulosis of the genitalia. A possible Koebner phenomenon. Int J Dermatol 1990; 29: 430–431. 4 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the penis. Cancer 1978; 42: 1890–1903. 5 Berger BW, Hori Y. Multicentric bowen’s disease of the genitalia: spontaneous regression of lesions. Arch Dermatol 1978; 114: 1698–1699.
Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. ... more Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. The action of anti-allergic agents from Psidium guajava (P. guajava) on T cell immunity in mice was investigated. The addition of P. guajava extracts blocked IL-10-mediated, in vitro induction of T regulatory (Tr) cells from CD4+ splenocytes of C57BL/6 mice, whereas the extracts exerted only a weak or no effect on the development of Th1 and Th2 cells. Accordingly, Tr cells were not induced from splenocytes of mice administered orally with the extracts. Furthermore, P. guajava extracts shifted the Th1/Th2 balance to a Th1 dominant status by directly attenuating Tr cell activity. In a study of tumor immunity, mice pretreated with the extracts exhibited retarded growth of s.c. inoculated B16 melanoma cells. These findings suggest that P. guajava extracts are efficacious for the prevention of tumor development by depressing Tr cells and subsequently shifting to Th1 cells.
from epidermal nevus cells, or arise from hair follicle keratinocytes accompanying the EN. Hafner... more from epidermal nevus cells, or arise from hair follicle keratinocytes accompanying the EN. Hafner et al. found that a biopsy containing both BCC and EN revealed E545K PIK3CA mutation which was present in the BCC rather than in the EN. In BCC samples, there have been no previously documented EN in any PIK3CA hotspot mutations although other regions mutations may exist. Moreover, a clonal relationship cannot be completely excluded because the BCC developed later than the EN. So, both lesions may still share a common but yet unknown molecular genetic alteration. However, due to our limited hospital conditions, further examination such as molecular analysis could not be implemented. The clinical features of our case were similar to those of the reported case by Hafner et al.. Despite having multiple, bilateral and asymmetrical lesions, our patient had no evidence of neurological disease such as mental retardation and seizures. In fact, malignant transformation of EN may occur whether or not they are associated with other organ system abnormalities. When sudden, localized development of nodules, erosions or ulcers appear, malignant transformation should be suspected. Li-qiang ZHENG, Yong HUANG, Yan-jing QU, Yuan-hong ZHANG, Xiang-chun HAN Departments of Dermatology, Pathology, 251st Hospital of Chinese PLA, and Department of Pathology, the First Affiliated Hospital to Hebei North University, Zhangjiakou City, China
Roxithromycin (RXM), a 14-member macrolide antibiotic, has a variety of bioregulatory functions s... more Roxithromycin (RXM), a 14-member macrolide antibiotic, has a variety of bioregulatory functions such as anti-inflammatory effects, anti-oxidant effects, and modulation of immune responses. In this study, we analyzed the effect of RXM on chemokine-induced chemotaxis of Th1, Th2, and regulatory T (Treg) cells established from three normal human peripheral blood lymphocytes by the reported methods. Incubation with 10 microM RXM for 18 h did not alter the expression profile of CXCR3 on Th1 cells and CCR4 on Th2 and Treg cells. However, upon RXM preincubation, the migration of Th1 cells to IP-10 and Th2 cells to TARC was partially suppressed, although RXM did not influence Treg cell migration. Erythromycin and clarithromycin at the same concentration did not exert such effects. F-actin polymerization and Ca(++) influx induced by IP-10 and TARC in Th1 and Th2 cells, respectively, was down-regulated by RXM pretreatment. These results imply that RXM exhibits bioregulatory function by influencing chemotaxis of Th1 and Th2 cells while leaving Treg cell migration unaffected.
Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 e... more Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 expression, F-actin polymerization and calcium influx in patients with alopecia areata Journal of Dermatological Science xxx (2013) xxx-xxx G Model DESC-2532; No. of Pages 4 Please cite this article in press as: Ito T, et al. Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 expression, F-actin polymerization and calcium influx in patients with alopecia areata.
Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cyt... more Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs). The HF is a unique “miniorgan” with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as “hair follicle immune privilege.” The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN). IFN-γis one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathog...
Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Rega... more Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells...
The Journal of allergy and clinical immunology, Jan 11, 2016
Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment ... more Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a TH17-mediated disorder, but the underlying mechanism remains unclear. We investigated the effect of this topical applicant, focusing on skin-infiltrating TH17 cells. In 10 patients with plaque psoriasis, calcipotriol (Cal), betamethasone dipropionate (Bet), or the calcipotriol and betamethasone dipropionate 2-compound formulation (CB) was applied to 3 different psoriatic plaques with similar severity once a day for 14 days. One nonapplied lesion was used as a control. Four-millimeter biopsy specimens were taken from each site, cut into 2 pieces, and subjected to histologic examination and ex vivo expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2. Clinical, histologic, and IL-17A(+) cell-infiltrate improvement was found in the following order: CB > Cal > Bet > control or CB > Bet > Cal > control. Numbers of ex vivo expanded T c...
Human T-cell lymphotropic virus type 1 (HTLV-1) induces adult T cell leukemia/lymphoma (ATLL), HT... more Human T-cell lymphotropic virus type 1 (HTLV-1) induces adult T cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. Approximately half of ATLL patients have direct skin involvement of neoplastic cells. However, there exist HTLV-1-associated reactive eruptions with a predominant infiltrate of non-neoplastic CD8+ T cells in ATLL, HAM/TSP and carrier. A 50-year-old Japanese female HTLV-1 carrier had several episodes of itchy, indurated erythema that occurred diffusely on the face and neck, lasted for 2 weeks and spontaneously subsided without sequelae. Histopathologically, CD3+ T cells infiltrated the upper dermis, and part of the infiltrating cells were CD4+CD25+, sharing the phenotype with ATLL neoplastic cells. An aggregate of CD8+ T cells bearing the cytotoxic molecule TIA-1 was also present. It is possible that skin-affinitive HTLV-1+CD4+ T cells propagated and subsequently disappeared as a result of cytotoxic T cell attack.
Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-... more Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4(+) CD25(+) CCR4(+) T-cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV-1. To clarify the presence of reactive skin eruptions in HTLV-1-infected individuals, we reviewed our patients with HTLV-1-associated diseases. In 2002-2012, we saw 50 ATLL or HAM/TSP patients and HTLV-1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8(+) T cells, but not CD4(+) tumor cells. The cases included erythroderma (HTLV-1 carrier), lichen planus (HTLV-1 carrier), alopecia a...
Poor agreement between self-reported and dermatologists' diagnoses for five common dermatoses. Br... more Poor agreement between self-reported and dermatologists' diagnoses for five common dermatoses. Br J Dermatol 2006;155:1006e12.
It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We ... more It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tapestripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholineinduced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.
The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Maj... more The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Major advances in our understanding of the autonomic and sensory transmission and function include the recognition of the phenotypic expression of a variety of transmitters and modulators that often coexist in individual neurons, the concept of co-transmission and chemical coding, the evidence for local effector functions of primary afferent nerves, and the discovery of plasticity of both the autonomic and the sensory nervous system during development, aging, diseases states, and inflammation. Co-transmission or plurichemical transmission, which indicates the release of more than one chemical messenger from the same neuron, enables autonomic and sensory neurons to exert a fine and highly regulated control of various functions such as circulation and immune response. The concept of chemical coding, in which the combination of transmitters/modulators is established, allows the identification of functional classes of neurons with their projections and targets. In addition to transmitters and modulators, autonomic and sensory neurons express multiple receptors, including G-proteincoupled and ion-gated receptors, further supporting the complexity of autonomic and sensory transmission and function. Autonomic neurons regulate the internal environment and maintain multiple homeostatic functions, and sensory neurons act as receptive structures that activate their targets in response to stimulation but also exert effector functions including the control of blood flow and vascular permeability, maintenance of mineralized tissue, and regulation of gene expression.
Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates an... more Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates and articular cartilage and has a key role in the biophysical and biomechanical properties of cartilage. Recently, heterozygous mutations in the ACAN gene, which encodes aggrecan, have been identified in patients with short stature and accelerated bone age. We herein report another family with a heterozygous ACAN mutation associated with idiopathic short stature along with accelerated bone age and early-onset herniation of the lumbar discs at the levels of L1/2 through L5/S1. Whole-exome sequencing identified a novel heterozygous frameshift mutation in the ACAN gene (c.1744delT; p.Phe582fs*69) in all of the affected family members but not in the unaffected one, providing further evidence that ACAN haploinsufficiency causes short stature with advanced bone maturation. In addition, we advocate early-onset multiple disc herniation as a novel phenotype associated with ACAN haploinsufficiency.
Spontaneous remission occurs in up to 80% of patients with limited patchy alopecia areata (AA) wi... more Spontaneous remission occurs in up to 80% of patients with limited patchy alopecia areata (AA) within 1 year. Therefore, not all patients of AA simplex/multiplex need extensive treatments, and "wait and see" is one of the choices for some patients. However, once the hair loss show progressive course, it is really difficult to manage well and may be recalcitrant to any treatment in some cases. Hair loss symptom is not life-threatening but severely decreases quality of life. There have been two widely known guidelines for AA from the British Association of Dermatologists and the National Alopecia Areata Foundation (USA). These guidelines have been substantial and provide clues for dermatologists but needed to be updated. Recently, the Japanese Dermatological Association also published a guideline for the management of AA. This guideline suggests treatments followed by recommendations and evidence levels. Several new treatments are added such as corticosteroid pulse therapy a...
1 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the genitalia. Arch Dermatol 1979; 115: 30... more 1 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the genitalia. Arch Dermatol 1979; 115: 306–308. 2 Patterson JW, Kao GF, Graham JH, Helwig EB. Bowenoid papulosis. A clinicopathologic study with ultrastructural observations. Cancer 1986; 57: 823–836. 3 Sweidan NA, Salman SM, Zaynoun ST, Sanaknaki BA, Kibbi AG. Linear bowenoid papulosis of the genitalia. A possible Koebner phenomenon. Int J Dermatol 1990; 29: 430–431. 4 Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the penis. Cancer 1978; 42: 1890–1903. 5 Berger BW, Hori Y. Multicentric bowen’s disease of the genitalia: spontaneous regression of lesions. Arch Dermatol 1978; 114: 1698–1699.
Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. ... more Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. The action of anti-allergic agents from Psidium guajava (P. guajava) on T cell immunity in mice was investigated. The addition of P. guajava extracts blocked IL-10-mediated, in vitro induction of T regulatory (Tr) cells from CD4+ splenocytes of C57BL/6 mice, whereas the extracts exerted only a weak or no effect on the development of Th1 and Th2 cells. Accordingly, Tr cells were not induced from splenocytes of mice administered orally with the extracts. Furthermore, P. guajava extracts shifted the Th1/Th2 balance to a Th1 dominant status by directly attenuating Tr cell activity. In a study of tumor immunity, mice pretreated with the extracts exhibited retarded growth of s.c. inoculated B16 melanoma cells. These findings suggest that P. guajava extracts are efficacious for the prevention of tumor development by depressing Tr cells and subsequently shifting to Th1 cells.
from epidermal nevus cells, or arise from hair follicle keratinocytes accompanying the EN. Hafner... more from epidermal nevus cells, or arise from hair follicle keratinocytes accompanying the EN. Hafner et al. found that a biopsy containing both BCC and EN revealed E545K PIK3CA mutation which was present in the BCC rather than in the EN. In BCC samples, there have been no previously documented EN in any PIK3CA hotspot mutations although other regions mutations may exist. Moreover, a clonal relationship cannot be completely excluded because the BCC developed later than the EN. So, both lesions may still share a common but yet unknown molecular genetic alteration. However, due to our limited hospital conditions, further examination such as molecular analysis could not be implemented. The clinical features of our case were similar to those of the reported case by Hafner et al.. Despite having multiple, bilateral and asymmetrical lesions, our patient had no evidence of neurological disease such as mental retardation and seizures. In fact, malignant transformation of EN may occur whether or not they are associated with other organ system abnormalities. When sudden, localized development of nodules, erosions or ulcers appear, malignant transformation should be suspected. Li-qiang ZHENG, Yong HUANG, Yan-jing QU, Yuan-hong ZHANG, Xiang-chun HAN Departments of Dermatology, Pathology, 251st Hospital of Chinese PLA, and Department of Pathology, the First Affiliated Hospital to Hebei North University, Zhangjiakou City, China
Roxithromycin (RXM), a 14-member macrolide antibiotic, has a variety of bioregulatory functions s... more Roxithromycin (RXM), a 14-member macrolide antibiotic, has a variety of bioregulatory functions such as anti-inflammatory effects, anti-oxidant effects, and modulation of immune responses. In this study, we analyzed the effect of RXM on chemokine-induced chemotaxis of Th1, Th2, and regulatory T (Treg) cells established from three normal human peripheral blood lymphocytes by the reported methods. Incubation with 10 microM RXM for 18 h did not alter the expression profile of CXCR3 on Th1 cells and CCR4 on Th2 and Treg cells. However, upon RXM preincubation, the migration of Th1 cells to IP-10 and Th2 cells to TARC was partially suppressed, although RXM did not influence Treg cell migration. Erythromycin and clarithromycin at the same concentration did not exert such effects. F-actin polymerization and Ca(++) influx induced by IP-10 and TARC in Th1 and Th2 cells, respectively, was down-regulated by RXM pretreatment. These results imply that RXM exhibits bioregulatory function by influencing chemotaxis of Th1 and Th2 cells while leaving Treg cell migration unaffected.
Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 e... more Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 expression, F-actin polymerization and calcium influx in patients with alopecia areata Journal of Dermatological Science xxx (2013) xxx-xxx G Model DESC-2532; No. of Pages 4 Please cite this article in press as: Ito T, et al. Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 expression, F-actin polymerization and calcium influx in patients with alopecia areata.
Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cyt... more Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs). The HF is a unique “miniorgan” with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as “hair follicle immune privilege.” The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN). IFN-γis one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathog...
Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Rega... more Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells...
The Journal of allergy and clinical immunology, Jan 11, 2016
Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment ... more Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a TH17-mediated disorder, but the underlying mechanism remains unclear. We investigated the effect of this topical applicant, focusing on skin-infiltrating TH17 cells. In 10 patients with plaque psoriasis, calcipotriol (Cal), betamethasone dipropionate (Bet), or the calcipotriol and betamethasone dipropionate 2-compound formulation (CB) was applied to 3 different psoriatic plaques with similar severity once a day for 14 days. One nonapplied lesion was used as a control. Four-millimeter biopsy specimens were taken from each site, cut into 2 pieces, and subjected to histologic examination and ex vivo expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2. Clinical, histologic, and IL-17A(+) cell-infiltrate improvement was found in the following order: CB > Cal > Bet > control or CB > Bet > Cal > control. Numbers of ex vivo expanded T c...
Human T-cell lymphotropic virus type 1 (HTLV-1) induces adult T cell leukemia/lymphoma (ATLL), HT... more Human T-cell lymphotropic virus type 1 (HTLV-1) induces adult T cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. Approximately half of ATLL patients have direct skin involvement of neoplastic cells. However, there exist HTLV-1-associated reactive eruptions with a predominant infiltrate of non-neoplastic CD8+ T cells in ATLL, HAM/TSP and carrier. A 50-year-old Japanese female HTLV-1 carrier had several episodes of itchy, indurated erythema that occurred diffusely on the face and neck, lasted for 2 weeks and spontaneously subsided without sequelae. Histopathologically, CD3+ T cells infiltrated the upper dermis, and part of the infiltrating cells were CD4+CD25+, sharing the phenotype with ATLL neoplastic cells. An aggregate of CD8+ T cells bearing the cytotoxic molecule TIA-1 was also present. It is possible that skin-affinitive HTLV-1+CD4+ T cells propagated and subsequently disappeared as a result of cytotoxic T cell attack.
Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-... more Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4(+) CD25(+) CCR4(+) T-cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV-1. To clarify the presence of reactive skin eruptions in HTLV-1-infected individuals, we reviewed our patients with HTLV-1-associated diseases. In 2002-2012, we saw 50 ATLL or HAM/TSP patients and HTLV-1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8(+) T cells, but not CD4(+) tumor cells. The cases included erythroderma (HTLV-1 carrier), lichen planus (HTLV-1 carrier), alopecia a...
Poor agreement between self-reported and dermatologists' diagnoses for five common dermatoses. Br... more Poor agreement between self-reported and dermatologists' diagnoses for five common dermatoses. Br J Dermatol 2006;155:1006e12.
It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We ... more It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tapestripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholineinduced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.
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Papers by Taisuke Ito