TY - JOUR
T1 - Cutting edge
T2 - Notch signaling promotes the plasticity of group-2 innate lymphoid cells
AU - Zhang, Kangning
AU - Xu, Xingyuan
AU - Pasha, Muhammad Asghar
AU - Siebel, Christian W.
AU - Costello, Angelica
AU - Haczku, Angela Franciska
AU - MacNamara, Katherine
AU - Liang, Tingbo
AU - Zhu, Jinfang
AU - Bhandoola, Avinash
AU - Maillard, Ivan
AU - Yang, Qi
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1601421
DO - 10.4049/jimmunol.1601421
M3 - Article
C2 - 28115527
AN - SCOPUS:85014897838
VL - 198
SP - 1798
EP - 1803
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -