Identification of novel stromal cell tyep regulating body cavity immunity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K22531
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University (2020-2022); Kyoto University (2019)
• Principal Investigator: Okabe Yasutaka 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (50522124)
• Project Period (FY): 2019-06-28 – 2023-03-31
• Keywords: 大網乳斑 / ストローマ細胞 / レチノイン酸

Outline of Final Research Achievements

Lymphoid clusters in visceral adipose tissue omentum, known as milky spots, play a central role in the immunological defense in the abdomen, whereas the mechanism regulating milky spot development and maturation are poorly understood. In this study, we identified a subset of fibroblastic reticular cells (FRCs) that are uniquely present in omental milky spots. These FRCs were characterized by the expression of retinoic acid converting enzyme, Aldh1a2, and endothelial cell marker, Tie2, in addition to canonical FRC-associated genes. Diphtheria toxin-mediated ablation of Aldh1a2+ FRCs resulted in the alteration in milky spot structure with a significant reduction in size and cellularity. Mechanistically, Aldh1a2+ FRCs regulated the display of chemokine CXCL12 on high endothelial venules (HEVs), which recruit blood-borne lymphocytes from circulation. We further found that Aldh1a2+ FRCs are required for the maintenance of peritoneal lymphocyte composition. These

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、腹腔内の病原体侵入の監視・応答を担う大網乳斑に特異的に存在する新しいストローマ細胞が同定されたとともに、これまでほとんど明らかにされてこなかった大網乳斑の形成メカニズムの一端が解明された。これらの知見は、腹腔内感染症および致死性の敗血症のメカニズムの理解や治療法の開発へ繋がる可能性が期待される。