神戸大学 · 農学研究科

研究关键词mucosal immunology・Peyer's patches・IgA production・gut commensal microbiota・intestinal tumorigenesis・follicle-associated epithelium・innate lymphoid cells・dietary antigens

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• Deep-sea water preserves depth-dependent water molecular network signatures after recovery2026 · 2026年05月, ChemRxiv, 英語
• 食餌誘導性肥満における自然リンパ球の機能解析2016 · 2016年03月, 日本語
• Role of leukotriene B4 (LTB4)-LTB4 receptor 1 signaling in post-incisional nociceptive sensitization and local inflammation in mice.Leukotriene B4 (LTB4) is a potent lipid mediator involved in the recruitment and activation of neutrophils, which is an important feature of tissue injury and inflammation. The biological effects of LTB4 are primarily mediated through the high-affinity LTB4 receptor, BLT1. Postoperative incisional pain is characterized by persistent acute pain at the site of tissue injury and is associated with local inflammation. Here, we compared the role of LTB4-BLT1 signaling in postoperative incisional pain between BLT1-knockout (BLT1KO) and wild-type (BLT1WT) mice. A planter incision model was developed, and mechanical pain hypersensitivity was determined using the von Frey test before and after incision. Local infiltration of neutrophils and inflammatory monocytes was quantified by flow cytometry. Inflammatory cytokine levels in the incised tissue were also determined. Mechanical pain hypersensitivity was significantly reduced in BLT1KO mice compared to BLT1WT mice at 2, 3, and 4 days after incision. LTB4 levels in the tissue at the incision site peaked 3 hours after the incision. Infiltrated neutrophils peaked 1 day after the incision in both BLT1KO and BLT1WT mice. The accumulation of inflammatory monocytes increased 1-3 days after the incision and was significantly more reduced in BLT1KO mice than in BLT1WT mice. In BLT1KO mice, Interleukin-1β and Tumor Necrosis Factor-α levels 1 day after the incision were significantly lower than those of BLT1WT mice. Our data suggest that LTB4 is produced and activates its receptor BLT1 in the very early phase of tissue injury, and that LTB4-BLT1 signaling exacerbates pain responses by promoting local infiltration of inflammatory monocytes and cytokine production. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.
• Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice.Gain-of-function (GOF) mutations in the gene for signal transducer and activator of transcription 1 (STAT1) account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. To tackle this problem, we introduced the human R274Q GOF mutation into mice [GOF-Stat1 knock-in (GOF-Stat1R274Q)]. To investigate the immune responses, we focused on the small intestine (SI), which contains abundant Th17 cells. Stat1R274Q/R274Q mice showed excess phosphorylation of STAT1 in CD4+ T cells upon IFN-γ stimulation, consistent with the human phenotype in patients with the R274Q mutation. We identified two subpopulations of CD4+ T cells, those with 'normal' or 'high' level of basal STAT1 protein in Stat1R274Q/R274Q mice. Upon IFN-γ stimulation, the 'normal' level CD4+ T cells were more efficiently phosphorylated than those from WT mice, whereas the 'high' level CD4+ T cells were not, suggesting that the level of STAT1 protein does not directly correlate with the level of pSTAT1 in the SI. Inoculation of Stat1R274Q/R274Q mice with Candida albicans elicited decreased IL-17-producing CD4+RORγt+ cells. Stat1R274Q/R274Q mice also excreted larger amounts of C. albicans DNA in their feces than control mice. Under these conditions, there was up-regulation of T-bet in CD4+ T cells. GOF-Stat1R274Q mice thus should be a valuable model for functional analysis of this disorder.

• 腸管免疫系における高度不飽和脂肪酸の機能解析 佐々木 崇晴 日本学術振興会, 科学研究費助成事業 基盤研究(C), 順天堂大学, 2023年04月 - 2026年03月2023 · KUID parsed section
• 肥満を誘導する自然リンパ球を介した腸内細菌機能制御機構の解析 佐々木 崇晴 公益財団法人 武田科学振興財団, 医学系研究助成（基礎）, 国立研究開発法人理化学研究所, 2021年08月 - 2024年03月, 研究代表者2021 · KUID parsed section
• 肥満における腸内細菌と自然リンパ球の相互作用解析 佐々木 崇晴 公益財団法人 上原記念生命科学財団, 研究奨励金, 国立研究開発法人理化学研究所, 2020年01月 - 2021年04月, 研究代表者2020 · KUID parsed section
• 自然リンパ球に注目した脂肪組織恒常性維持機構の解明 小安 重夫, 茂呂 和世, 佐々木 崇晴 日本学術振興会, 科学研究費助成事業 基盤研究(A), Grant-in-Aid for Scientific Research (A), 国立研究開発法人理化学研究所, 2016年04月 - 2019年03月 獲得免疫系を欠くRag2-/-マウスと、自然リンパ球を含む全てのリンパ球を欠損するγc-/-Rag2-/-マウスを用い、高脂肪食負荷を与えた際の体重増加に、小腸粘膜固有層由来の2型自然リンパ球（SI-ILC2）と3型自然リンパ球（SI-ILC3）が関与し、これらのILCが産生するIL-2が必要である事を明らかにした。一方、脂肪組織由来のILC2（WAT-ILC2）はSI-ILC2と異なる性質を持ち、前脂肪細胞から脂肪細胞への分化を抑制する活性を持つことを明らかにした。2016 · KUID parsed section

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