Kumiko Taguchi

Langerhans Cells Serve as Immunoregulatory Cells by Activating NKT Cells

Ultraviolet exposure alters the morphology and function of epidermal Langerhans cells (LCs), which play a role in UV-induced immune suppression. It is generally believed that UV exposure triggers the migration of immature LCs from the skin to the draining lymph nodes (LNs), where they induce tolerance. However, because most of the previous studies employed in vitro UV-irradiated LCs, the data generated may not adequately reflect what is happening in vivo. In this study, we isolated migrating LCs from the LNs of UV-irradiated mice and studied their function. We found prolonged LC survival in the LNs of UV-irradiated mice. LCs were necessary for UV-induced immune suppression because no immune suppression was observed in LC-deficient mice. Transferring LCs from UV-irradiated mice into normal recipient animals transferred immune suppression and induced tolerance. We found that LCs colocalized with LN NKT cells. No immune suppression was observed when LCs were transferred from UV-irradiated mice into NKT cell-deficient mice. NKT cells isolated from the LNs of UV-irradiated mice secreted significantly more IL-4 than NKT cells isolated from nonirradiated controls. Injecting the wild-type mice with anti–IL-4 blocked the induction of immune suppression. Our findings indicate that UV exposure activates the migration of mature LC to the skin draining LNs, where they induce immune regulation in vivo by activating NKT cells.

Rapid Desensitization with Autologous Sweat in Cholinergic Urticaria

BACKGROUND The majority of patients with cholinergic urticaria presents with strong hypersensitivity to autologous sweat. Patients with severe cholinergic urticaria are frequently resistant to H(1) antagonists which are used in conventional therapies for various types of urticaria. It has been reported that desensitization using partially purified sweat antigen was effective in a patient with cholinergic urticaria. METHODS The aim of this study is to determine the usefulness of rapid desensitization with autologous sweat in severe cholinergic urticaria, because rapid desensitization has proven to be a quick and effective immunotherapy for allergies to various allergens. Six patients with severe cholinergic urticaria who are resistant to H(1) antagonists and have sweat hypersensitivity were enrolled in a rapid desensitization protocol. RESULTS In all six patients, the responses for skin tests with autologous sweat were attenuated after rapid desensitization with autologous sweat. Two of the three cholinergic urticaria patients showed reduced histamine release with autologous sweat after the rapid desensitization with autologous sweat. Further, the rapid desensitization and subsequent maintenance treatment reduced the symptoms in five of the six patients. CONCLUSIONS This study provides evidence that rapid desensitization with autologous sweat is beneficial for treating cholinergic urticaria patients resistant to conventional therapy who have sweat hypersensitivity.

Anti-Inflammatory Role of Langerhans Cells and Apoptotic Keratinocytes in Ultraviolet-B–Induced Cutaneous Inflammation

UV radiation, particularly UVB, is the major risk factor for the induction of skin cancer, and it induces skin inflammation and immunosuppression. Although reports documented that Langerhans cells (LCs) play various roles in photobiology, little is known about whether they contribute to UVB-induced cutaneous inflammation. Recently, the anti-inflammatory effect of apoptotic cells was noted. This study focuses on the roles of LCs and apoptotic cells in UVB-induced cutaneous inflammation. We show that LCs are essential for resolution of UVB-induced cutaneous inflammation. Administration of quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone, a broad-spectrum caspase inhibitor with potent antiapoptotic properties, inhibited the formation of UVB-induced apoptotic cells and aggravated UVB-induced cutaneous inflammation in wild-type mice. In contrast, exacerbation of UVB-induced cutaneous inflammation following quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone administration was not observed in LC-depleted mice. These results suggest that the interaction between LCs and apoptotic cells is critical for resolution of UVB-induced cutaneous inflammation. Interestingly, UVB-induced apoptotic keratinocytes were increased in LC-depleted mice. In addition, we revealed that UVB-induced apoptotic keratinocytes were phagocytosed by LCs ex vivo and that prolongation of UVB-induced cutaneous inflammation following treatment with Cytochalasin D, an inhibitor of phagocytosis, was partially attenuated in LC-depleted mice. Collectively, our findings demonstrate that the interaction between LCs and apoptotic cells, possibly via LC-mediated phagocytosis of apoptotic keratinocytes, has an essential anti-inflammatory role in the resolution of UVB-induced cutaneous inflammation.

UVB Exposure Prevents Atherosclerosis by Regulating Immunoinflammatory Responses

Objective— UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. Approach and Results— Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4+ forkhead box P3+ regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell–depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4+ forkhead box P3+ regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. Conclusions— Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.

Eccrine angiomatous hamartoma with sudden enlargement and pain in an adolescent girl after menarche.

Eccrine angiomatous hamartoma (EAH) is a rare, benign cutaneous lesion characterized histologically by a proliferation of eccrine glands and vascular structures—generally capillaries—in the middle and deep dermis. Sudden enlargement of EAH lesions with or without pain has been noted during puberty and pregnancy and has been attributed to hormonal stimulation. We herein describe a case of EAH that became symptomatic in an adolescent girl. A 13-year-old girl presented with pain associated with a sudden enlargement of a previously asymptomatic swelling on her right second toe. She had an 8-year history of an asymptomatic swelling on her right second toe, and the symptoms appeared approximately 1 year after menarche. Physical examination revealed swelling of the plantar surface of her right second toe. The overlying surface was erythematous with a small amount of fine scales. The biopsied tissue showed a nodular proliferation of eccrine glands intimately admixed with numerous small vessels in the deep dermis and subcutaneous fat tissue. Mucin deposition was present in the stroma surrounding the proliferating eccrine coils and ducts and in the upper dermis. A diagnosis of EAH was made. We suggest that hormonal changes during puberty may have played a role in the rapid growth and pain in the present case.

Aspirin-intolerant chronic urticaria exacerbated by cutaneous application of a ketoprofen poultice.

© 2010 The Authors. doi: 10.2340/00015555-0901 Journal Compilation

Acute generalized exanthematous pustulosis induced by Mycoplasma pneumoniae infection.

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The Rho kinase pathway regulates the migration of dendritic cells through SIRP-α

Dendritic cells (DCs) are professional antigen-presenting cells PCs) capable of initiating innate and acquired immune sponses. In peripheral tissues including the skin, they reside immature DCs and process foreign antigens. After capturing tigens, cutaneous DCs, including Langerhans cells (LCs) and the ligation of SIRP-a and that the migration of LCs is impaired in SIRP-a mutant mice that lack the intracellular domain of SIRP-a [1]. Moreover, we reported that the CHS response is markedly attenuated in mice treated with an anti-SIRP-a mAb before sensitization and in SIRP-a mutant mice. Those reports suggest that SIRP-a plays a critical role in the motility of cutaneous DCs and is thus essential for the development of CHS. The small GTPase Rho plays critical roles in the regulation of va by le [3 DC