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Identification of two migratory colon ILC2 populations differentially expressing IL-17A and IL-5/IL-13

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Abstract

Group 2 innate lymphoid cells (ILC2s) play important tissue resident roles in anti-parasite immunity, allergic immune response, tissue homeostasis, and tumor immunity. ILC2s are considered tissue resident cells with little proliferation at steady state. Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues, circulate and migrate to different organs, including lung, liver, mesenteric LN and spleen, upon activation. However, it remains unknown whether other ILC populations with migratory behavior exist. In this study, we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation. One subset expresses IL-17A and resembles inflammatory ILC2s (iILC2s) but lacks CD27 expression, whereas the other expresses CD27 but not IL-17A. In addition, the IL-17A+ ILC2s express lower levels of CD127, CD25, and ST2 than CD27+ ILC2s, which express higher levels of IL-5 and IL-13. Surprisingly, we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27, IL-5/IL-13, respectively. Together, our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31930035, 91942311, 32061143028), Shanghai Science and Technology Commission (20410714000) and the National Key Research and Developmental Program of China (2021YFA1301400). We would like to thank Renyan Wu for processing the raw sequencing data; Drs. Hongxiang Sun and Ziyang Xu for assisting with RNA-seq data analysis. We also thank the generous support from Flow cytometry Core and Sequencing Core at Shanghai Institute of Immunology and animal facility of Shanghai Jiao Tong University School of Medicine.

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Authors and Affiliations

  1. Shanghai Institute of Immunology, Department of Immunology and Microbiology, the Ministry of Education Key Laboratory of Cell Death and Differentiation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Hongzhi Liu, Liang Li, Zhaoyuan Liu, Jingjing Qi, Jingjing Zhang, Ningbo Wu, Dandan Wu, Caixia Gao, Lei Chen, Lei Shen & Bing Su

  2. Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Hongzhi Liu, Yanyun Hao & Jinke Cheng

  3. State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, 200001, China

    Jialu Li

  4. Department of Biliary and Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Jingjing Qi

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  1. Hongzhi Liu
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Liu, H., Li, L., Hao, Y. et al. Identification of two migratory colon ILC2 populations differentially expressing IL-17A and IL-5/IL-13. Sci. China Life Sci. 66, 67–80 (2023). https://doi.org/10.1007/s11427-022-2127-2

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