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Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis

Cellular & Molecular Immunology volume 19, pages 869–871 (2022)Cite this article

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Innate lymphoid cells are predominantly tissue-resident immune cells that have diverse functions similar to T-cell subsets and regulate tissue homeostasis and innate immunity without specific antigen recognition. Previous studies have reported the important roles of type 2 innate lymphoid cells (ILC2s) in allergic inflammation, such as those in asthma and food allergies, and shown that ILC2s play key roles in chronic inflammatory diseases, including pulmonary fibrosis and autoimmune disease [1, 2]. Tissue- and disease-specific innate immune cells, including ILC2s, have been shown to be important in the development of various other diseases [3,4,5]. In a study published in Nature Immunology, Zhang et al. revealed that neuropilin-1 (NRP1) is a specific marker for lung ILC2s and coordinates ILC2 functions in fibrotic lungs without affecting ILC2s in other tissues [6].

ILC2s localize to various tissues throughout the body, including adipose tissue and the lungs, intestines, skin, bone marrow, brain, and muscles. ILC2s produce type 2 cytokines, such as interleukin (IL)-4, IL-5, IL-9, IL-13, and amphiregulin, which are related to tissue repair, fibrosis, and innate immunity. ILC2s express receptors for thymic stromal lymphopoietin, IL-25, and IL-33, which are produced by epithelial and vascular endothelial cells damaged by environmental factors, including infectious agents and allergens at barrier surfaces. NRP1 was identified as a cell-surface receptor involved in the development of the cardiovascular system, pathogenic angiogenesis, vascular permeability, and organogenesis outside the nervous system. Several binding partners of NRP1 have been identified, including semaphorin 3A, vascular endothelial growth factor-α, and transforming growth factor (TGF)β1. NRP1 is expressed by various types of immune cells; however, its expression in ILC2s is largely uncharacterized.

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Acknowledgements

We thank Susan Zunino, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported, in part, by AMED (grant numbers JP20fk0108129, JP21fk0108129h0702, and JP21lm0203007), a GSK Research grant (grant number A-32), JSPS KAKENHI (grant numbers JP21K16118 and JP21K08194), the Smoking Research Foundation (grant number 2021Y007), the Takeda Science Foundation, the Uehara Memorial Foundation (grant number 202110055), the MSD Life Science Foundation (grant number RA-026), the Japanese Respiratory Society Boehringer Ingelheim Research Grant Program, and the Japan Intractable Diseases (Nanbyo) Research Foundation (grant number 2020B02).

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Authors and Affiliations

  1. Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Osaka, Japan

    Takuro Nii, Kiyoharu Fukushima & Hiroshi Kida

  2. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan

    Kiyoharu Fukushima & Hiroshi Kida

  3. Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan

    Kiyoharu Fukushima

  4. Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Osaka, 565-0871, Japan

    Kiyoharu Fukushima

  5. Global Center for Medical Engineering and Informatics, 2-2 Yamadaoka, Suita, Osaka, Japan

    Kiyoharu Fukushima

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Correspondence to Hiroshi Kida.

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The authors declare that they have no competing financial interests. The funders had no role in the writing of the manuscript or in the decision to publish the results.

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Nii, T., Fukushima, K. & Kida, H. Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis. Cell Mol Immunol 19, 869–871 (2022). https://doi.org/10.1038/s41423-022-00867-0

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