Elucidation of the molecular mechanism underlying the regulation of fibrosis-inducing-pathogenic CD4+ T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03685
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Chiba University
• Principal Investigator: Hirahara Kiyoshi 千葉大学, 大学院医学研究院, 教授 (00707193)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 病原性CD4+ T細胞 / single cell RNA-Seq / ATAC-Seq / 慢性炎症

Outline of Final Research Achievements

We identified a group of genes that cause quantitative changes in fibrosis-induced-pathogenic CD4+ T cells. We have generated a gene-deficient mouse and a reporter mouse for one of these genes. We found; (1) CD4+ T cells from the gene-deficient mouse were markedly reduced in the lungs. (2) CD4+ T cells expressing the gene were frequently infiltrated in the nasal polyps of human eosinophilic sinusitis patients. The results of this study not only revealed a new function of pathogenic helper T cells in pathogenesis, but also identified a new molecular mechanism for their regulation. Based on the results of this study, we will continue our research to elucidate new regulatory mechanisms of CD4+ T cells that are deeply involved in the pathogenesis of chronic inflammatory diseases and to form the technological basis for the development of novel therapies for intractable allergic airway diseases for which there is no curative treatment.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

今回の研究結果は、病原性ヘルパーT細胞の病態形成における新たな機能を明らかにしただけでなく、その制御に関わる新たな分子機構を同定した。今後、本研究成果をもとに、慢性炎症疾患病態形成に深く関与するCD4+ T細胞の新たな制御機構が明らかになり、根治的治療法のない難治性アレルギー性気道疾患の新規治療法開発の技術基盤を形成すべく研究を続ける。