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Kinetics of the accumulation of group 2 innate lymphoid cells in IL-33-induced and IL-25-induced murine models of asthma: a potential role for the chemokine CXCL16

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Yan Li, Shihao Chen, Yafei Chi, Yiran Yang, Xiwen Chen, Huating Wang, Zhe Lv, Jingjing Wang, Linjie Yuan, Ping Huang, Kewu Huang, Chris J. Corrigan, Wei Wang, Sun Ying

Original languageEnglish
Pages (from-to)75-86
Number of pages12
JournalCellular and Molecular Immunology
Issue number1
Early online date22 Nov 2018
E-pub ahead of print22 Nov 2018
Published1 Jan 2019

King's Authors


ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways. We investigated the time course of ILC2 accumulation in different tissues in murine models of asthma induced by a serial per-nasal challenge with ovalbumin (OVA), house dust mice (HDM), IL-25 and IL-33 and explored the potential roles of ILC2-attracting chemokines in this phenomenon. Flow cytometry was used to enumerate ILC2s at various time points. The effects of cytokines and chemokines on ILC2 migration were measured in vitro using a chemotaxis assay and in vivo using small animal imaging. Compared with saline and OVA challenge, both IL-25 and IL-33 challenge alone induced significant accumulation of ILC2s in the mediastinal lymph nodes, lung tissue and bronchoalveolar lavage fluid of challenged animals, but with a distinct potency and kinetics. In vitro, IL-33 and CXCL16, but not IL-25 or CCL25, directly induced ILC2 migration. Small animal in vivo imaging further confirmed that a single intranasal provocation with IL-33 or CXCL16 was sufficient to induce the accumulation of ILC2s in the lungs following injection via the tail vein. Moreover, IL-33-induced ILC2 migration involved the activation of ERK1/2, p38, Akt, JNK and NF-κB, while CXCL16-induced ILC2 migration involved the activation of ERK1/2, p38 and Akt. These data support the hypothesis that epithelium-derived IL-25 and IL-33 induce lung accumulation of ILC2s, while IL-33 exerts a direct chemotactic effect in this process. Although ILC2s express the chemokine receptors CXCR6 and CCR9, only CXCL16, the ligand of CXCR6, exhibits a direct chemoattractant effect.

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