2022 Fiscal Year Final Research Report

IL-15-producing microenvironment supporting innate lymphoid cells and its role in diseases

Research Project

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Project/Area Number	20H03501
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 49070:Immunology-related
Research Institution	Kyoto University
Principal Investigator	Ikuta Koichi 京都大学, 医生物学研究所, 教授 (90193177)
Co-Investigator(Kenkyū-buntansha)	榛葉旭恒京都大学, 医学研究科, 助教 (30812242) 谷一靖江京都大学, 医学研究科, 特定講師 (50432331) 崔广為京都大学, 医生物学研究所, 助教 (70791276)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	自然免疫 / サイトカイン / 微小環境 / IL-15 / 腫瘍免疫
Outline of Final Research Achievements	Innate-like lymphocytes such as NK and NKT cells play pivotal roles in infectious immune responses, antitumor immunity, and inflammatory immune diseases. In this study, we identified IL-15-producing cells that support the differentiation, maintenance, and function of NK and NKT cells and clarified their functions. First, we demonstrated the reliance of NK cells on IL-15 derived from hematopoietic cells within the bone marrow for their differentiation. Furthermore, we have discerned two distinct subsets of bone marrow NK cells: scattered and clustered, with CXCL12 emerging as a critical factor in the distribution of the scattered population. Additionally, we have established the dependence of CD244+ iNKT cells on IL-15 produced by thymic epithelial cells for their differentiation. Notably, this subset exhibits elevated levels of IFN-g, akin to NK cells, and plays an important role in tumor cell elimination.
Free Research Field	免疫学
Academic Significance and Societal Importance of the Research Achievements	自然免疫系リンパ球は、感染免疫応答、抗腫瘍免疫、炎症免疫疾患において重要な働きをしているが、その分化や機能を支える微小環境については不明であった。本研究では、NK細胞が骨髄造血細胞のIL-15に依存して分化する発見から、造血細胞の分化を他の造血細胞が支持するという新規概念の提唱に発展した。また、散在型とクラスター型の２種類のNK細胞の発見から、NK細胞が機能の異なるサブセットに分かれている可能性が想起された。さらに、CD244陽性iNKT細胞は通常型iNKT細胞とは異なり全身循環性であることから、iNKT細胞も機能的に異なるサブセットに分かれている可能性が示された。