Research of the association between the graft-versus-host disease related dry eye disease and the PD-1/PD-L1 pathway

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18358
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: Hayashi Shunsuke 慶應義塾大学, 医学部(信濃町), 助教 (50837771)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: GVHD

Outline of Final Research Achievements

During this research period, we conducted histopathological examinations of the cornea and lacrimal gland in a cGVHD mouse model, revealing neovascularization and cellular infiltration. Furthermore, immunocompetent cell infiltration, predominantly by CD4-positive T cells, was observed in pseudomembranes from patients with overlapping GVHD. Analysis of splenic tissue from GVHD model mice using FACS showed that 80% of CD4-positive T cells expressed PD-1. Subsequent fluorescent immunostaining in the lacrimal gland confirmed infiltration of PD-1-positive CD4-positive T cells. These findings suggest the potential involvement of PD-1-positive CD4-positive T cells and CD153-positive cells in epithelial cells of the GVHD lacrimal gland. Based on these results, we are currently exploring new therapeutic targets for this condition.

Free Research Field

GVHD

Academic Significance and Societal Importance of the Research Achievements

慢性GVHDの症例には高度なドライアイや眼表面炎症が合併する。GVHD発症後には酸化ストレス増加や危険シグナル増加などの複合的要因による慢性刺激によって、非感染性の慢性炎症が惹起され遷延化すると考えられる。cGVHDに関連した眼表面のGVHDヒト涙腺においてPD-1/PD-L1経路の関与が考えられたため、PD-1分子、PD-L1分子の局在を検討することで同分子の発現の機序やGVHD病態への関わり、分子メカニズムを追求しようと着想し研究を実施した。根治的な標準治療が存在しない本疾患に対して、PD1PDL1分子が新たな治療標的となる可能性がある。