Cutting edge: Notch signaling promotes the plasticity of group-2 innate lymphoid cells

Kangning Zhang, Xingyuan Xu, Muhammad Asghar Pasha, Christian W. Siebel, Angelica Costello, Angela Franciska Haczku, Katherine MacNamara, Tingbo Liang, Jinfang Zhu, Avinash Bhandoola, Ivan Maillard, Qi Yang

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands induced Rorc expression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes.

Original languageEnglish (US)
Pages (from-to)1798-1803
Number of pages6
JournalJournal of Immunology
Volume198
Issue number5
DOIs
StatePublished - Mar 1 2017

ASJC Scopus subject areas

  • Immunology

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    Zhang, K., Xu, X., Pasha, M. A., Siebel, C. W., Costello, A., Haczku, A. F., MacNamara, K., Liang, T., Zhu, J., Bhandoola, A., Maillard, I., & Yang, Q. (2017). Cutting edge: Notch signaling promotes the plasticity of group-2 innate lymphoid cells. Journal of Immunology, 198(5), 1798-1803. https://doi.org/10.4049/jimmunol.1601421