Regulation of allergic and autoimmune responses by ILC2-T cell interaction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08766
• 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: Tohoku University
• Principal Investigator: Ishii Naoto 東北大学, 医学系研究科, 教授 (60291267)
• Co-Investigator(Kenkyū-buntansha): 宗 孝紀 富山大学, 学術研究部薬学・和漢系, 教授 (60294964)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 2型自然リンパ球 / 腫瘍免疫 / アトピー性皮膚炎

Outline of Final Research Achievements

We found that OX40-L is expressed on IL-33-stimulated group 2 innate lymphoid cells (ILC2) in mice and may exert anti-tumor effects by providing OX40 stimulation to killer T cells, an important finding indicating an immune activation mechanism through the interaction between ILC2 and T cells.
We also found that OX40 expression on peripheral blood ILC2 of adult patients with atopic dermatitis was higher than that of healthy subjects. Furthermore, we found that the expression level of OX40 is positively correlated with the POEM score, an index of the severity of atopic dermatitis. The increased proliferation and expression of Th2 cytokines in in vitro OX40-stimulated ILC2 suggests that OX40-expressing ILC2 may be involved in the pathogenesis of atopic dermatitis.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

OX40はT細胞に活性化シグナルを伝達する共刺激分子として知られており、人為的なOX40阻害はアレルギー・自己免疫疾患の治療標的であり、OX40刺激はヒトにおいても抗腫瘍効果を発揮する。OX40-OX40L系がILC2の活性化やT細胞との相互作用で機能するとの本知見は学術的にも臨床医学的にも重要な発見である。