Gene expression analysis by RNA-Seq and development of novel therapeutic target in IgG4-related disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: University of Tsukuba
• Principal Investigator: Tsuboi Hiroto 筑波大学, 医学医療系, 准教授 (80580505)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: IgG4関連疾患 / RNA-Seq / 顎下腺 / 末梢血単核球 / T細胞 / B細胞

Outline of Final Research Achievements

We conducted RNA sequencing to compare the gene expressions of T and B cells in submandibular glands (SMGs) and peripheral blood mononuclear cells (PBMCs) in IgG4-related disease (IgG4-RD) or IgG4-RD versus primary Sjogren's syndrome (pSS) and healthy controls (HCs) in PBMCs. Principal component analysis (PCA) results showed the gene expression patterns of T and B cells derived from SMGs differed from those derived from PBMCs in IgG4-RD. The upregulated differentially expressed genes (DEGs) in SMGs of IgG4-RD included cytokines, chemokines, and transcription regulators such as IL-21 and EGR2. Ingenuity pathway analysis (IPA) for these DEGs clarified that Th1, Th2, IL-17, wound healing, Toll-like Receptor (TLR), and systemic lupus erythematosus (SLE) signaling for T cells, while IL-8, IL-15, complement, fibrosis, and SLE signaling for B cells were positively regulated in SMGs compared with PBMCs in IgG4-RD.

Free Research Field

膠原病内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、RNA-SeqによりIgG4関連疾患（IgG4-RD）の唾液腺病変局所のT/B細胞で発現変動した遺伝子が抽出され、病態への寄与が示唆されるパスウェイが同定された。これらの遺伝子やパスウェイは、IgG4-RDの新規診断マーカーや治療標的となる可能性が期待される。また、現在開発が進行中のIgG4-RDの分子標的治療薬の好適症例の同定や、治療反応性予測にも貢献できる可能性がある。