UTO Tomofumi

写真a

Affiliation

Faculty of Medicine School of Medicine Department of Infectious Diseases, Immunology

Title

Associate Professor

External Link

Degree 【 display / non-display

  • 博士(医学) ( 2007.5   鹿児島大学 )

Research Areas 【 display / non-display

  • Life Science / Immunology

 

Papers 【 display / non-display

  • Mechanism on antigen delivery under mucosal vaccination using cell-penetrating peptides immobilized at multiple points on polymeric platforms. Reviewed

    Ukawa M, Endo R, Yagi H, Tomono T, Miyata K, Shigeno K, Tobita E, Uto T, Baba M, Sakuma S

    International journal of pharmaceutics   613   121376   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ijpharm.2021.121376

    PubMed

  • Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation Reviewed

    Nishikawa Y., Fukaya T., Fukui T., Uto T., Takagi H., Nasu J., Miyanaga N., Riethmacher D., Choijookhuu N., Hishikawa Y., Amano M., Sato K.

    Frontiers in Immunology   12   712676   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers in Immunology  

    Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

    DOI: 10.3389/fimmu.2021.712676

    Scopus

    PubMed

  • Characterization of bovine interleukin-2 stably expressed in HEK-293 cells. Reviewed

    Mitoma S, El-Khaiat HM, Uto T, Sato K, Sekiguchi S, Norimine J

    The Journal of veterinary medical science   83 ( 1 )   134 - 141   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:公益社団法人 日本獣医学会  

    <p>Interleukin 2 (IL-2) is a pleotropic cytokine and well-known as a T cell growth factor in immunology. It is now known to exert both immunostimulatory and immunosuppressive effects, optimizing immunological microenvironments for effector and regulatory T cell responses. The immunomodulatory role of IL-2 is critical for deciding whether or not T cell responses against specific antigens result in protection. We have established a mammalian cell line (HEK-293) stably expressing bovine IL-2 (boIL-2) (designated as HEK-293/boIL-2), using the piggyBac transposon system. The concentration of recombinant bovine IL-2 (rboIL-2) in the culture supernatant of HEK-293/boIL-2 reached 100 ng/ml on day 7 and showed similar proliferative activity to recombinant human IL-2 (rhuIL-2) for bovine peripheral mononuclear blood cells. Although rhuIL-2 has been often used to activate bovine T cells, our results indicate that characteristics of the T cell activation through rboIL-2 and huIL-2 appear slightly but significantly different. Interestingly, the rboIL-2/anti-boIL-2 monoclonal antibody (C5) (rboIL-2/C5) complex strongly induced proliferation of bovine NKp46<sup>+</sup>cells, natural killer (NK) cells, <i>in vitro</i>. This indicates that the rboIL-2/C5 complex could function as an IL-2 agonist specifically to increase the NK cell population, which in turn could enhance the activity of NK cells leading to protective immunity.</p>

    DOI: 10.1292/jvms.20-0423

    PubMed

  • Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy Reviewed

    Miyanaga N., Takagi H., Uto T., Fukaya T., Nasu J., Fukui T., Nishikawa Y., Sparwasser T., Choijookhuu N., Hishikawa Y., Nakamura T., Tono T., Sato K.

    Communications Biology   3 ( 1 )   742   2020.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Communications Biology  

    © 2020, The Author(s). While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.

    DOI: 10.1038/s42003-020-01466-3

    Scopus

    PubMed

  • Pivotal role of CD103 in the development of psoriasiform dermatitis Reviewed

    Fukui T., Fukaya T., Uto T., Takagi H., Nasu J., Miyanaga N., Nishikawa Y., Koseki H., Choijookhuu N., Hishikawa Y., Yamashita Y., Sato K.

    Scientific Reports   10 ( 1 )   8371   2020.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

    © 2020, The Author(s). The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis.

    DOI: 10.1038/s41598-020-65355-9

    Scopus

    PubMed

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Books 【 display / non-display

  • Current Topics in Microbiology and Immunology

    Sato, K. Uto, T., Fukaya, T., and Takagi, H.( Role: Joint author)

    Springer Publishing  2017.9 

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    Total pages:47-71   Language:English Book type:Scholarly book

    Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines. On the other hand, treatment of DCs with certain immunosuppressive drugs and molecules leads to the generation of tolerogenic DCs that show downregulation of both the major histocompatibility complex (MHC) and costimulatory molecules, and not only show defective T-cell activation, but also possess tolerogenic properties including the induction of anergic T-cells and regulatory T (Treg) cells. To develop an effective strategy for Ag-specific intervention of T-cell-mediated immune disorders, we have previously established the modified DCs with moderately high levels of MHC molecules that are defective in the expression of costimulatory molecules that had a greater immunoregulatory property than classical tolerogenic DCs, which we therefore designated as regulatory DCs (DCreg). Herein, we integrate the current understanding of the role of DCs in the control of immune responses, and further provide new information of the characteristics of tolerogenic DCs and DCreg, as well as their regulation of immune responses and disorders.

  • Methods in Molecular Biology

    Fukaya, T., Takagi, H., Uto, T, Arimura, K., and Sato, K.( Role: Joint author)

    Springer Publishing  2016.5 

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    Total pages:291-308   Responsible for pages:291-308   Language:English Book type:Scholarly book

MISC 【 display / non-display

  • 経口免疫寛容の誘導における形質細胞様樹状細胞の役割 Invited Reviewed

    佐藤克明, 宇都倫史, 高木秀明,深谷知宏

    臨床免疫・アレルギー科   71 ( 2 )   134 - 137   2019.2

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:科学評論社  

  • 樹状細胞サブセットによる免疫制御機構 Invited

    佐藤克明, 宇都倫史, 深谷知宏, 高木秀明

    臨床免疫・アレルギー科   67 ( 6 )   539 - 544   2017.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:科学評論社  

  • 樹状細胞サブセットと免疫応答制御 Invited Reviewed

    佐藤克明, 宇都倫史, 深谷知宏, 高木秀明

    炎症と免疫   25 ( 3 )   71 - 77   2017.4

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:先端医学社  

  • 樹状細胞サブセットとその機能

    佐藤克明, 宇都倫史, 深谷知広, 高木秀明

    臨床免疫・アレルギー科   63 ( 6 )   563 - 568   2015.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:科学評論社  

Presentations 【 display / non-display

  • Clec4A4 acts as immune checkpoint molecule expressed on conventional dendritic cells to suppress tumor immunity

    宇都倫史、深谷知宏、高木秀明、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会学術集会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Oral presentation (general)  

  • Gut dysbiosis abrogates the protective effect of oral tolerance through the dysfunction of CD103+ cDCs in mesenteric lymph nodes

    深谷知宏、宇都倫史、高木秀明、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会学術集会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Poster presentation  

  • Plasmacytoid dendritic cells potentiate an effective anti-tumor immunity by preventing T-cell exhaustion

    高木秀明、宇都倫史、深谷知宏、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会学術集会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Poster presentation  

  • Requirement of gut mucosal plasmacytoid dendritic cells for establishing oral tolerance to prevent undesirable allergic disorders

    宇都倫史、高木秀明、深谷知宏、奈須遵太、福井丈仁、宮永宜明、西川陽太郎、佐藤克明

    第48回日本免疫学会総会  (アクトシティ浜松)  日本免疫学会

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    Event date: 2019.12.13

    Language:English   Presentation type:Poster presentation  

    Venue:アクトシティ浜松  

  • Essential role of submandibular lymph node conventional dendritic cells in the protective effect of sublingual immunotherapy on allergic asthma

    高木秀明、宮永宜明、宇都倫史、深谷知宏、奈須遵太、福井丈仁、西川陽太郎、佐藤克明

    第48回日本免疫学会総会  (アクトシティ浜松)  日本免疫学会

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    Event date: 2019.12.13

    Language:English   Presentation type:Poster presentation  

    Venue:アクトシティ浜松  

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Grant-in-Aid for Scientific Research 【 display / non-display

  • ヒト樹状細胞を標的とした新規免疫チェックポイント阻害剤の開発

    Grant number:20K07703  2020.04 - 2023.03

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  • 新規免疫チェックポイント分子Clec4A4によるがん免疫制御機構の解明

    2017.04 - 2020.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator