The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation

Morris Nechama, Jeahoo Kwon, Shuo Wei, Adrian Tun Kyi, Robert S. Welner, Iddo Z. Ben-Dov, Mohamed S. Arredouani, John M. Asara, Chun Hau Chen, Cheng Yu Tsai, Kyle F. Nelson, Koichi S. Kobayashi, Elliot Israel, Xiao Zhen Zhou, Linda K. Nicholson, Kun Ping Lu

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Interleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling. Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. Thus, the IL-33-PIN1-IRAK-M is an axis critical for dendritic cell activation, type 2 immunity and IL-33 induced airway inflammation.

Original languageEnglish
Article number1603
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018
Externally publishedYes

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