Role of monocyte and macrophage in chronic GVHD

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Okayama University
• Principal Investigator: Maeda Yoshinobu 岡山大学, 医歯薬学総合研究科, 教授 (60403474)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 慢性GVHD

Outline of Final Research Achievements

Chronic graft-versus-host disease (GVHD) is the main cause of late death and morbidity after allogeneic stem cell transplantation (SCT). Fibrosis constitutes the end stage of the inflammatory process in chronic GVHD leading to major morbidity. Recently, segregated-nucleus-containing atypical monocytes (SatM) that involved in lung fibrosis has been identified. Ly6clow monocyte, Ly6c+ monocyte and SatM increased in BALF of allogeneic recipient. In the sclerodermatous chronic GVHD model, SatM increased in ear of allogeneic group. From these results, we hypothesized that SatM may cause the fibrosis of chronic GVHD. To demonstrate that SatM causes the fibrosis of chronic GVHD, we established GVHD model with SatM deficiency mouse (Cebpb-/- mouse). Recipient of SatM deficiency mouse showed exacerbated GVHD, suggesting that Cebpb-/- donor cells have decreased regulatory function.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

慢性GVHDの予防・治療薬としてこれまでT細胞を抑制する薬剤が使用されてきたが、十分な効果を発揮できていない。本研究により慢性GVHD、特に肺病変における単球・マクロファージの関与が明らかとなった。SatM (Segregatd-nucleus-containing atypical monocytes)と名付けられたLy6C- 単球のなかでもCeacam1+, MSR1+の集団が肺合併症に関与することが示唆された。また、C/EBPbが移植後の免疫抑制に関与することも明らかとなった。これにより治療のターゲットが明らかとなり新規治療薬の開発に繋がる。