Role of AIF-1 in pathogenesis of pulmonary fibrosis and development of its treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09900
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KAWAHITO YUTAKA 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50336731)
• Co-Investigator(Kenkyū-buntansha): 河野 正孝 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60405256)
• Research Collaborator: NAGAHARA HIDETAKE ; KIDA TAKASHI
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: AIF-1 / 肺線維症 / ブレオマイシン

Outline of Final Research Achievements

AIF-1 is expressed in BALF in acute phase of bleomycin induced lung injury mouse model. TNF-α and IL-6 secreted from AIF stimulated macrophages and lung fibroblasts caused inflammation and tissue destruction. KC (CXCL1) is secreted form AIF stimulated lung fibroblasts inducing chemotaxis. In the chronic phase, AIF-1 is expressed in macrophages, secreting TGF-β, which is a growth factor involved in fibrosis. AIF-1 has the ability to proliferate and migrate lung fibroblasts. In addition, macrophage dendritic cells knockdown the AIF-1 gene were co-cultured with T cells, it was revealed that T cell proliferation due to nonspecific antigen stimulation was suppressed. Thus, it is suggested that AIF-1 is involved in the pathogenesis of acute and chronic stages of pulmonary fibrosis.

Free Research Field

膠原病・リウマチ性疾患

Academic Significance and Societal Importance of the Research Achievements

肺線維化の免疫反応を含めたメカニズムは未だ不明であり、リウマチ性疾患合併症として間質性肺炎から生じる肺線維症有効な治療法がなく難治性であり、生命予後を悪化させる。近年、AIF-1は、ヒトの全身性硬化症の間質性肺病変や線維化皮膚病変での発現がみられているが、繊維化に関わる機序は明らかにされていなかった。本研究では、AIF-1が、マクロファージや肺線維芽細胞からサイトカインやケモカインを誘導し、線維化に関与する増殖因子であるTGF-βを分泌することにより、肺の線維化の病因に深く関与する事が明らかになり、肺線維化治療の新たなターゲット分子になる可能性を示した。