The investigation of regulatory mechanisms for innate allergy by IL4-induced NK cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15737
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kiniwa Tsuyoshi 国立研究開発法人理化学研究所, 生命医科学研究センター, 基礎科学特別研究員 (90793795)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: NK cell / ILC2 / TFH / IL-4 / Allergy

Outline of Final Research Achievements

In this study, we investigated the physiological roles of IL-4 induced NK cell (IL4-NK) in allergic diseases using mouse model of asthma. Especially, we focused on the interactions among T follicular helper (TFH), Group 2 innate lymphoid cells (ILC2), and IL4-NK. We found that serum IgE was reduced by injecting a depleting antibody against NK cells into asthmatic mice. Because IgE is induced by IL-4 from TFH, this result suggested that NK cell can suppress TFH during asthmatic diseases. Furthermore, we revealed that ILC2 co-cultured with IL4-NK showed lower proliferation and cytokine production compared to without IL4-NK, suggesting that IL4-NK can suppressed ILC2 directly.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、アレルギー病態における新たなNK細胞の制御機構およびその生理的役割として、IL-4を受け取ったNK細胞が活性化し、TFHやILC2と相互作用しそれらを抑制することでアレルギー性炎症の過剰な亢進を抑制する、ネガティブフィードバック機構に働く可能性があることが明らかになった。IL4-NKの誘導機序やTFHおよびILC2を抑制する機構の詳細は今の所不明であるが、今後その詳細が明らかとなれば、あらたなアレルギー性疾患の治療法開発の糸口となることが期待できる。