Updated on 2025/06/23

Information

 

写真a

 
KAWATA KAZUHIKO
 
Organization
Medical Institute of Bioregulation Department of Immunobiology and Neuroscience Assistant Professor
Title
Assistant Professor

Papers

  • Critical roles of chronic BCR signaling in the differentiation of anergic B cells into age-associated B cells in aging and autoimmunity International journal

    Imabayashi, K; Yada, Y; Kawata, K; Yoshimura, M; Iwasaki, T; Baba, A; Harada, A; Akashi, K; Niiro, H; Baba, Y

    SCIENCE ADVANCES   11 ( 16 )   eadt8199   2025.4   ISSN:2375-2548

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Science Advances  

    Age-associated B cells (ABCs) with autoreactive properties accumulate with age and expand prematurely in autoimmune diseases. However, the mechanisms behind ABC generation and maintenance remain poorly understood. We show that continuous B cell receptor (BCR) signaling is essential for ABC development from anergic B cells in aged and autoimmune mice. ABCs exhibit constitutive BCR activation, with surface BCRs being internalized. Notably, anergic B cells, but not nonautoreactive B cells, contributed to ABC formation in these models. Anergic B cells also showed a greater propensity for in vitro differentiation into ABCs, which was inhibited by the expression of the transcription factor Nr4a1. Bruton’s tyrosine kinase (Btk), a key BCR signaling component, was constitutively activated in ABCs from aged and autoimmune mice as well as patients with lupus. Inhibiting Btk reduced ABC numbers and ameliorated the pathogenicity of lupus mice. Our findings reveal critical mechanisms underlying ABC development and offer previously unrecognized therapeutic insights for autoimmune diseases.

    DOI: 10.1126/sciadv.adt8199

    Web of Science

    Scopus

    PubMed

  • Bruton's tyrosine kinase inhibition limits endotoxic shock by suppressing IL-6 production by marginal zone B cells in mice Reviewed International journal

    Kawata, K; Hatano, S; Baba, A; Imabayashi, K; Baba, Y

    FRONTIERS IN IMMUNOLOGY   15   1388947   2024.4   ISSN:1664-3224

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

    Sepsis is a systemic inflammatory response to a severe, life-threatening infection with organ dysfunction. Although there is no effective treatment for this fatal illness, a deeper understanding of the pathophysiological basis of sepsis and its underlying mechanisms could lead to the development of new treatment approaches. Here, we demonstrate that the selective Bruton’s tyrosine kinase (Btk) inhibitor acalabrutinib augments survival rates in a lipopolysaccharide (LPS)-induced septic model. Our in vitro and in vivo findings both indicate that acalabrutinib reduces IL-6 production specifically in marginal zone B (MZ B) cells rather than in macrophages. Furthermore, Btk-deficient MZ B cells exhibited suppressed LPS-induced IL-6 production in vitro. Nuclear factor-kappa B (NF-κB) signaling, which is the downstream signaling cascade of Toll-like receptor 4 (TLR4), was also severely attenuated in Btk-deficient MZ B cells. These findings suggest that Btk blockade may prevent sepsis by inhibiting IL-6 production in MZ B cells. In addition, although Btk inhibition may adversely affect B cell maturation and humoral immunity, antibody responses were not impaired when acalabrutinib was administered for a short period after immunization with T-cell-independent (TI) and T-cell-dependent (TD) antigens. In contrast, long-term administration of acalabrutinib slightly impaired humoral immunity. Therefore, these findings suggest that Btk inhibitors may be a potential option for alleviating endotoxic shock without compromising humoral immunity and emphasize the importance of maintaining a delicate balance between immunomodulation and inflammation suppression.

    DOI: 10.3389/fimmu.2024.1388947

    Web of Science

    Scopus

    PubMed

Presentations

Research Projects

  • 液性免疫応答における小胞体恒常性の生理的役割

    Grant number:22KJ2457  2023.3 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for JSPS Fellows

    河田 和彦

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    Authorship:Principal investigator  Grant type:Scientific research funding

    液性免疫応答は生体防御のメカニズムとして重要である。液性免疫の主役を担うのはB細胞であり、B細胞の小胞体恒常性維持がB細胞分化と抗体産生に密接に関与する。小胞体はタンパク質の品質管理と細胞質内Ca2+濃度の調節が主な機能として知られており、これら2つの機能を制御することが小胞体恒常性に重要である。そこで細胞内及び小胞体カルシウム濃度の調節と複数回膜貫通型タンパク質の恒常性に重要である分子EMC1に着目し、B細胞における機能解析を行う。これにより、液性免疫における小胞体恒常生の生理学的役割の解明を目指す。

    CiNii Research