Pannexin 3 provides bone marrow niche for B- and T cell differentiation.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22698
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Tohoku University
• Principal Investigator: Ishikawa Masaki 東北大学, 大学病院, 助教 (60432936)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 骨髄幹細胞 / 骨髄ニッチ / 免疫細胞分化 / Gap junction / Pannexin

Outline of Final Research Achievements

Bone has been defined as an endocrine organ to regulate physiological functions in many tissues. Bone marrow stem cell niche plays important roles for hematopoietic cell differentiation and maintenance. However, the mechanisms and component of bone marrow niche are not fully understood. Pannexin 3 (Panx3), a member of gap junction protein family is predominately expressed in hard tissue such as bone, cartilage and tooth. Panx3 inhibits precursor cell proliferation and promotes differentiation by its small molecule permeable channel functions. Still, Panx3 functios in bone marrow, especially as bone marrow niche is not known. Here, we describe that Panx3 KO mice revealed the skeletal dysplasia, enlarged thymus and shrunken spleen. Further, B- and T cell maturation in Panx3 KO mice were insufficient. Thus, our findings suggest that Panx3 regulates B- and T cell differentiation by Panx3-provided bone marrow niche.

Free Research Field

歯科保存学

Academic Significance and Societal Importance of the Research Achievements

今研究で硬組織特異的Gap junction 膜タンパクPanx3が形成する骨髄微小環境、ニッチがB細胞およびT細胞の分化を制御することを明らかにした。この結果は新しい骨髄ニッチの存在を示し、骨環境に新たな免疫細胞形成機構があることを示唆するもので、学術的に新しい扉を開けるものとなった。また、Gap junctionによる骨髄ニッチは初の報告であり、細胞生物学的にも新しい発見と言える。今回の発見は骨生理“骨を中心とした全身の恒常性維持機構”をより解明するものであり、今後さらなる免疫細胞の維持および分化機構を明らかにすることで新治療法開発にも波及する可能性を示した。