Elucidation of novel regulatory mechanisms of allergy and inflammation by paired immune receptors recognizing llipids

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03721
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: kitaura Jiro 順天堂大学, 大学院医学研究科, 教授 (30282651)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アレルギー / 炎症 / ペア型免疫受容体

Outline of Final Research Achievements

We performed binding and reporter assays using an extracellular domain of leukocyte mono-immunoglobulin-like receptor (LMIR), which belongs to paired immune receptor family, to identify the LMIR ligands included in foreign bodies. We found that an activating receptor LMIR5 recognized the water-soluble molecule contained in Aspergillus, a type of fungus. In addition, intranasal administration of aqueous solution, containing this molecule, induced airway and lung inflammation by acting on LMIR5 expressed on myeloid cells. On the other hand, we identified the unknown lipid ligands for both an activating receptor LMIR5 and an inhibitory receptor LMIR3 that were included in ragweed pollen. Thus, LMIR recognized specific ligands included in the foreign bodies, thereby possibly regulating allergy and inflammation.

Free Research Field

アレルギー・炎症

Academic Significance and Societal Importance of the Research Achievements

ペア型免疫受容体は生体内外の分子を認識して免疫を制御すると想定されるが、その全貌は明らかになっていない。本研究により、ペア型免疫受容体の一つであるLMIR分子はアスペルギルス真菌やブタクサ花粉に含まれる生体外分子を認識することが判明した。これらの結果は、LMIRが生体外分子を認識してアレルギー・炎症・感染を制御する可能性を示しており、本研究成果の学術的意義は高い。さらに、本研究成果はアレルギー・炎症・感染に対する治療法開発につながる可能性を有し、社会的意義も高いと考えられる。