Mikami, Yohei



School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) (Shinanomachi)


Associate Professor

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Academic Degrees 【 Display / hide

  • PhD (Medicine), Keio University, Coursework, 2012


Research Keywords 【 Display / hide

  • Inflammatory bowel disease

  • Mucosal immunology

  • Tissue regeneration and fibrosis

  • Neuroimmunology


Papers 【 Display / hide

  • Severe graft-versus-host disease-like enterocolitis accompanied with cytomegalovirus-reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms

    Takamiyagi S., Iriki H., Asahina Y., Furuichi Y., Funakoshi T., Ichikawa M., Mikami Y., Okita H., Sakiyama T., Inazumi T., Amagai M., Takahashi H.

    Journal of Dermatology (Journal of Dermatology)  49 ( 8 ) 796 - 799 2022.08

    ISSN  03852407

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    Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug adverse reaction with skin eruption and visceral organ involvement. The characteristic clinical features of DIHS/DRESS are reactivation of human herpesviruses (HHV) and the development of autoimmune diseases, but their pathogenesis and associations are not yet understood. Here, we report a 66-year-old man who presented with fever, generalized erythema, diffuse lymphadenopathy, and diarrhea after 3 weeks of treatment with zonisamide. Reactivation of HHV-6 and cytomegalovirus (CMV) was detected during the clinical course. The patient was diagnosed with DIHS/DRESS and treated with systemic prednisolone, i.v. immunoglobulin therapy, and ganciclovir. However, severe enterocolitis persisted for 6 months. A series of examinations revealed features of both CMV enterocolitis, as indicated by identification of a few CMV-positive cells on immunohistochemical analysis, and graft-versus-host disease (GVHD)-like enterocolitis indicated by orange-peel appearance on endoscopic examination and histopathological loss of goblet cells. Intractable enterocolitis continued and the patient finally died of pneumonia. An autoimmune predisposition in DIHS/DRESS patients in combination with CMV reactivation was considered to trigger the severe enterocolitis of this case that showed GVHD-like features of the gastrointestinal tract. GVHD-like organ damage is a pathological condition rarely observed in DIHS/DRESS but should be recognized as one of the most severe complications of the disease.

  • Neuroimmune crosstalk in the gut and liver

    Teratani Toshiaki, Mikami Yohei, Kanai Takanori


    ISSN  0953-8178

  • Efficacy of Calcineurin Inhibitors for Induction of Remission in Intestinal Behçet's Disease

    Kawaguchi T., Fukata M., Omori T., Kiyohara H., Sugimoto S., Nanki K., Sujino T., Mikami Y., Kanai T.

    Crohn's and Colitis 360 (Crohn's and Colitis 360)  4 ( 3 )  2022.07

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    Background: The efficacy of calcineurin inhibitors (CNIs) for induction of remission in intestinal Behçet's disease (intestinal BD) has not been explored. Methods: A multicenter retrospective case series study of patients with active intestinal BD treated with CNIs (cyclosporin and tacrolimus) was conducted. Results: Of 16 patients, 12 (75%) showed a clinical response and 5 (31.3%) achieved clinical remission after 2 weeks of CNI treatment. Similar efficacy of CNIs was observed even in 7 patients refractory to antitumor necrosis factor-alpha therapies. Endoscopic improvement was observed in 11 of 12 patients. Conclusions: CNIs may be promising treatment options for refractory intestinal BD.

  • Heterogeneity of ILC2s in the Intestine; Homeostasis and Pathology

    Sunaga S., Tsunoda J., Teratani T., Mikami Y., Kanai T.

    Frontiers in Immunology (Frontiers in Immunology)  13   867351 2022.05

    ISSN  1664-3224

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    Group 2 innate lymphoid cells (ILC2s) were identified in 2010 as a novel lymphocyte subset lacking antigen receptors, such as T-cell or B-cell receptors. ILC2s induce local immune responses characterized by producing type 2 cytokines and play essential roles for maintaining tissue homeostasis. ILC2s are distributed across various organs, including the intestine where immune cells are continuously exposed to external antigens. Followed by luminal antigen stimulation, intestinal epithelial cells produce alarmins, such as IL-25, IL-33, and thymic stromal lymphopoietin, and activate ILC2s to expand and produce cytokines. In the context of parasite infection, the tuft cell lining in the epithelium has been revealed as a dominant source of intestinal IL-25 and possesses the capability to regulate ILC2 homeostasis. Neuronal systems also regulate ILC2s through neuropeptides and neurotransmitters, and interact with ILC2s bidirectionally, a process termed “neuro-immune crosstalk”. Activated ILC2s produce type 2 cytokines, which contribute to epithelial barrier function, clearance of luminal antigens and tissue repair, while ILC2s are also involved in chronic inflammation and tissue fibrosis. Recent studies have shed light on the contribution of ILC2s to inflammatory bowel diseases, mainly comprising ulcerative colitis and Crohn’s disease, as defined by chronic immune activation and inflammation. Modern single-cell analysis techniques provide a tissue-specific picture of ILC2s and their roles in regulating homeostasis in each organ. Particularly, single-cell analysis helps our understanding of the uniqueness and commonness of ILC2s across tissues and opens the novel research area of ILC2 heterogeneity. ILC2s are classified into different phenotypes depending on tissue and phase of inflammation, mainly inflammatory and natural ILC2 cells. ILC2s can also switch phenotype to ILC1- or ILC3-like subsets. Hence, recent studies have revealed the heterogeneity and plasticity of ILC2, which indicate dynamicity of inflammation and the immune system. In this review, we describe the regulatory mechanisms, function, and pathological roles of ILC2s in the intestine.

  • Aryl hydrocarbon receptor signals in epithelial cells govern the recruitment and location of Helios<sup>+</sup> Tregs in the gut

    Yoshimatsu Y., Sujino T., Miyamoto K., Harada Y., Tanemoto S., Ono K., Umeda S., Yoshida K., Teratani T., Suzuki T., Mikami Y., Nakamoto N., Sasaki N., Takabayashi K., Hosoe N., Ogata H., Sawada K., Imamura T., Yoshimura A., Kanai T.

    Cell Reports (Cell Reports)  39 ( 6 ) 110773 2022.05

    ISSN  2211-1247

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    CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Epithelium Replacement Contributes to Field Expansion of Squamous Epithelium and Ulcerative Colitis–Associated Neoplasia

    Sugimoto S., Iwao Y., Shimoda M., Takabayashi K., Sato T., Kanai T., Mutaguchi M., Nanki K., Okabayashi K., Kawaida M., Aoki Y., Yoshimatsu Y., Kiyohara H., Kawaguchi T., Mikami Y., Fukuhara K., Sujino T., Hosoe N., Ogata H., Yahagi N.

    Gastroenterology (Gastroenterology)  162 ( 1 ) 334 - 337.e5 2022.01

    ISSN  00165085

  • Primary granulocytic sarcoma of the small intestine diagnosed by single-balloon enteroscopy: A case report

    Ono K., Mikami Y., Hosoe N.

    Digestive Endoscopy (Digestive Endoscopy)  32 ( 3 ) 436 - 436 2020.03

    ISSN  09155635

  • Innate lymphoid cells in organ fibrosis

    Mikami Y., Takada Y., Hagihara Y., Kanai T.

    Cytokine and Growth Factor Reviews (Cytokine and Growth Factor Reviews)  42   27 - 36 2018.08

    ISSN  13596101

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    © 2018 Elsevier Ltd Innate lymphoid cells (ILCs) are a recently identified family of lymphoid effector cells. ILCs are mainly clustered into 3 groups based on their unique cytokine profiles and transcription factors typically attributed to the subsets of T helper cells. ILCs have a critical role in the mucosal immune response through promptly responding to pathogens and producing large amount of effector cytokines of type 1, 2, or 3 responses. In addition to the role of early immune responses against infections, ILCs, particularly group 2 ILCs (ILC2), have recently gained attention for modulating remodeling and fibrosis especially in the mucosal tissues. Herein, we overview the current knowledge in this area, highlighting roles of ILCs on fibrosis in the mucosal tissues, especially focusing on the gut and lung. We also discuss some new directions for future research by extrapolating from knowledge derived from studies on Th cells.

  • GoldiRunx and Remembering Cytotoxic Memory

    Mikami Y., Kanno Y.

    Immunity (Immunity)  48 ( 4 ) 614 - 615 2018.04

    ISSN  10747613

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    © 2018 The molecular basis for T cell memory differentiation remains elusive. Wang et al. (2018) identify Runx3 as an initiating transcription factor that specifies regulatory regions required for cytotoxic T cell (CTL) memory differentiation early after TCR signaling and constrains the ability of T-bet to drive terminal effector generation. The molecular basis for T cell memory differentiation remains elusive. Wang et al. (2018) identify Runx3 as an initiating transcription factor that specifies regulatory regions required for cytotoxic T cell (CTL) memory differentiation early after TCR signaling and constrains the ability of T-bet to drive terminal effector generation.

Presentations 【 Display / hide


    Puchner, Antonia, Saferding, Victoria, Bonelli, Michael, Mikami, Yohei, Goncalves-Alves, Eliana, Binder, Nikolaus B., Steiner, Carl-Walter, Hayer, Silvia, Niederreiter, Birgit, Koenders, Marije M., Smolen, Josef S., Redlich, Kurt, Bluml, Stephan



Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of the entropy of tissue damage in digestive organs and development of new therapeutic approaches


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Transformative Research Areas (B), Principal investigator

  • 炎症性組織レジリエンスと組織障害エントロピーの統合的理解と炎症収束学の創成


    Grants-in-Aid for Scientific Research, Grant-in-Aid for Transformative Research Areas (B), No Setting

  • 宿主侵入菌に対する腸管免疫応答を介した消化器免疫難病の病態解明


    Keio University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A), No Setting

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  • Gene regulation in the gut T cells and IBD


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

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  • 腸管Tリンパ球における体内時計と増殖代謝


    Keio University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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Awards 【 Display / hide

  • 第55回日本消化器免疫学会総会 奨励賞


    Type of Award: Award from Japanese society, conference, symposium, etc.

  • 三四会奨励賞

    2011, Keio University School of Medicine, Sanshikai

    Type of Award: Keio commendation etc.


Courses Taught 【 Display / hide





  • 内科学(消化器)【症例検討】下部消化管疾患

    2022, Seminar

  • 内科学(消化器)講義

    2022, Lecture



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