Momoko Kimishima
Kyorin University
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Publication
Featured researches published by Momoko Kimishima.
Journal of Immunology | 2009
Ryo Takahashi; Yoko Kano; Yoshimi Yamazaki; Momoko Kimishima; Yoshiko Mizukawa; Tetsuo Shiohara
Toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) represent two ends of a spectrum of severe drug eruptions: DIHS is unique in that severe epidermal damage seen in TEN is absent, sequential reactivations of herpesviruses occur, and autoimmunity often ensues. To investigate whether changes in regulatory T (Treg) cell function would contribute to variability in the clinical manifestations, we examined the frequency, phenotype, and function of Treg cells both during the acute stage and again long after clinical resolution of both diseases. Dramatic expansions of functional Treg cells were found in the acute stage of DIHS. In contrast, Treg function was profoundly impaired in TEN, although present in normal frequency. Skin homing addressins were more preferentially expressed on Treg cells in DIHS than in TEN. Indeed, Treg cells were more abundantly present in the skin lesions of DIHS. Surprisingly, Treg cells contracted upon resolution of DIHS became functionally deficient, whereas their functional defects in TEN were restored upon recovery. These findings indicate that a transitory impairment in their function during the acute stage of TEN may be related to severe epidermal damage, while a gradual loss of their function after resolution of DIHS may increase the risk of subsequently developing autoimmune disease.
Journal of Immunology | 2006
Michie Katsuta; Yukio Takigawa; Momoko Kimishima; Miyuki Inaoka; Ryo Takahashi; Tetsuo Shiohara
Innate immune cells mediate a first line of defense against pathogens and determine the nature of subsequent acquired immune responses, mainly by producing profound amounts of cytokines. Given these diverse tasks, it is predictable that defective NK and γδ+ T cell responses could be the underlying mechanism for the immunological alterations observed in atopic dermatitis (AD). Indeed, the frequencies of circulating NK cells and γδ+ T cells were profoundly reduced in AD patients. They also displayed a defective ability to sustain TNF-α and IFN-γ, but not IL-4, production after in vitro stimulation, and the defect was restricted to innate immune cells. Surprisingly, on the depletion of CD14+ monocytes, this selective impairment of TNF-α and IFN-γ production was restored to levels comparable to that observed in controls. Release of IL-10 from monocytes was not a major mechanism of the NK and γδ+ T cell dysfunction. Apoptosis as revealed by annexin V binding, was preferentially observed in NK and γδ+ T cells from AD patients when stimulated in the presence of monocytes, and depletion of monocytes significantly protected these cells from apoptotic cell death. Preferential apoptosis of NK cells by activated monocytes in AD patients was cell-contact-dependent. These results indicate that, once NK and γδ+ T cells in AD patients are in immediate contact with activated monocytes, these cells are specifically targeted for apoptosis, leading to the reduced type 1 cytokine production, thereby directing subsequent acquired immune responses toward a type-2 pattern and increasing susceptibility to infection.
Clinical and Experimental Dermatology | 2010
Kazuhisa Hirahara; Yoko Kano; Yoko Mitsuyama; Ryo Takahashi; Momoko Kimishima; Tetsuo Shiohara
Background. Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug–induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS).
Experimental Dermatology | 2006
Miyuki Inaoka; Momoko Kimishima; Ryo Takahashi; Tetsuo Shiohara
Abstract: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are known to be risk factors for a systemic inflammatory syndrome in viral infections. Innate immune cells are likely to represent the preferential targets for the deleterious effects of NSAIDs in patients with viral infections. We therefore examined whether various classes of NSAIDs could selectively inhibit cytokine production by innate immune cells. NSAIDs selectively inhibited interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α production by natural killer (NK) and γδ T cells with each NSAID displaying its own unique pattern of inhibition, while sparing that by acquired immune cells. These inhibitions were independent on cyclooxygenase inhibition. These NSAIDs directly inhibited the cytokine production by the purified γδ T‐cell population without involving other cell populations. The selective inhibition of the early generation of IFN‐γ and TNF‐α from NK and γδ T cells by NSAIDs may serve to drive the subsequent acquired immune responses towards a Th2 phenotype, leading to the aggravation of allergic symptoms. Our results provide a mechanism to explain the deleterious effects of NSAIDs on clinical symptoms of viral infections and allergic diseases and suggest more targeted use depending on the type of disease.
Journal of Immunology | 2014
Ryo Takahashi; Yohei Sato; Maiko Kurata; Yoshimi Yamazaki; Momoko Kimishima; Tetsuo Shiohara
It remains unknown why the occurrence of eczema herpeticum (EH) caused by an extensive disseminated cutaneous infection with HSV-1 or HSV-2 is associated with the exacerbation of atopic dermatitis lesions after withdrawal of treatment. Although regulatory T cells (Tregs) limit the magnitude of HSV-specific T cell responses in mice, their role in the induction and resolution of EH has not been defined. We initially investigated the frequencies, phenotype, and function of Tregs in the peripheral blood of atopic dermatitis with EH (ADEH) patients at onset and after clinical resolution, atopic dermatitis patients without EH, and healthy controls. Tregs with the skin-homing phenotype and the activated/induced phenotype were expanded at onset and contracted upon resolution. Treg-suppressive capacity was retained in ADEH patients and, the expanded Tregs suppressed IFN-γ production from HSV-1–specific CD8+ and CD4+ T cells. The increased frequency of CD14dimCD16+ proinflammatory monocytes (pMOs) was also observed in the blood and EH skin lesions. Thus, pMOs detected in ADEH patients at onset were characterized by an increased ability to produce IL-10 and a decreased ability to produce proinflammatory cytokines, unlike their normal counterparts. Our coculture study using Tregs and pMOs showed that the pMOs can promote the expansion of inducible Tregs. Tregs were detected frequently in the vicinity of HSV-expressing and varicella zoster virus–expressing CD16+ monocytes in the EH lesions. Expansions of functional Tregs, together with pMOs, initially required for ameliorating excessive inflammation occurring after withdrawal of topical corticosteroids could, in turn, contribute to the initiation and progression of HSV reactivation, resulting in the onset of EH.
Experimental Dermatology | 2008
Yoshiko Mizukawa; Ryo Takahashi; Yoshimi Yamazaki; Momoko Kimishima; Tetsuo Shiohara
Abstract: Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well‐recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E‐selectin but the epitope generated by fucosyltransferase VII (Fuc‐TVII) and because skin‐homing T cells are composed of three distinct subpopulations; Fuc‐TVII+ E‐selectin ligand (ESL)+ CLA−, Fuc‐TVII+ ESL+ CLA+ and Fuc‐TVII− ESL− CLA+ cells. We therefore asked which subpopulations of skin‐homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc‐TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin‐homing T cells with the potent capacity to migrate into the skin by analysing their Fuc‐TVII expression and E‐selectin binding ability in patients with AD.
Clinical & Experimental Allergy | 2018
Yukiko Ushigome; Yoshiko Mizukawa; Momoko Kimishima; Yoshimi Yamazaki; Ryo Takahashi; Yoko Kano; Tetsuo Shiohara
Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a distinct phenotype of severe drug eruptions characterized by sequential reactivations of herpesviruses. Although a progressive loss of suppressive function in regulatory T cells (Tregs) occurred during the course of DiHS/DRESS, but not in Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), no previous studies investigated the mechanism. Given the recent finding that Treg development could be differentially regulated by CD16+ patrolling monocytes (pMOs) and CD14+ classical monocytes (cMOs), we can hypothesize that a differential fine‐tuned interaction between Tregs and monocytes is the driving force behind the possible shift from Tregs to Th17 cells over a prolonged period of time in DiHS/DRESS.
The Journal of Allergy and Clinical Immunology | 2007
Habib Hasannejad; Ryo Takahashi; Momoko Kimishima; Kazuhito Hayakawa; Tetsuo Shiohara
Journal of Immunology | 1999
Hideki Kitagaki; Momoko Kimishima; Yuichi Teraki; Jun Hayakawa; Kazuhito Hayakawa; Shigeki Fujisawa; Tetsuo Shiohara
Journal of Investigative Dermatology | 2018
Yohei Sato; Ryo Takahashi; Momoko Kimishima; Yoshimi Yamazaki; Manabu Ohyama