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Invariant natural killer T cells and iron metabolism orchestrate skin development and homeostasis

Cellular & Molecular Immunology (2023)Cite this article

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In recent years, innate-like T-cell populations, such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells, have been identified [1]. These cells are different from conventional T cells in that they reside in tissues such as the liver, lung, and skin, rather than the lymph node and spleen [2]. Although iNKT and MAIT cells are abundant in the skin immediately after birth, the detailed functions or the mechanisms regulating their localization have not been clarified [3]. In a study published in Nature Immunology, Wang et al. reported that the early homing of iNKT cells to the skin was dependent on CCR10 expression during the stage of thymic development and was critical for proper commensal bacterial colonization and skin development [4].

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Fig. 1

References

  1. Mayassi T, Barreiro LB, Rossjohn J, Jabri B. A multilayered immune system through the lens of unconventional T cells. Nature. 2021;595:501–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Slauenwhite D, Johnston B. Regulation of NKT cell localization in homeostasis and infection. Front Immunol. 2015;6:255.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Constantinides MG, Belkaid Y. Early-life imprinting of unconventional T cells and tissue homeostasis. Sience. 2021;374:eabf0095.

    Article  CAS  Google Scholar 

  4. Wang WB, Lin YD, Zhao L, Liao C, Zhang Y, Davila M, et al. Developmentally programmed early-age skin localization of iNKT cells supports local tissue development and homeostasis. Nat Immunol. 2023;24:225–38.

    Article  CAS  PubMed  Google Scholar 

  5. Pellicci DG, Koay HF, Berzins SP. Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol. 2020;20:756–70.

    Article  CAS  PubMed  Google Scholar 

  6. Yang J, Restori KH, Xu M, Song EH, Zhao L, Hu S, et al. Preferential perinatal development of skin-homing NK1.1+ innate lymphoid cells for regulation of cutaneous microbiota colonization. iScience. 2020;23:101014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010;142:24–38.

    Article  CAS  PubMed  Google Scholar 

  8. Fukushima K, Satoh T, Sugihara F, Sato Y, Okamoto T, Mitsui Y, et al. Dysregulated expression of the nuclear exosome targeting complex component Rbm7 in nonhematopoietic cells licenses the development of fibrosis. Immunity. 2020;52:542–56.e13.

    Article  CAS  PubMed  Google Scholar 

  9. Niitsu T, Fukushima K, Komukai S, Takata S, Abe Y, Nii T, et al. Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease. RMD Open. 2023;9:e002667.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ali MK, Kim RY, Brown AC, Donovan C, Vanka KS, Mayall JR, et al. Critical role for iron accumulation in the pathogenesis of fibrotic lung disease. J Pathol. 2020;251:49–62.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank 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), the Japan Intractable Diseases (Nanbyo) Research Foundation (grant number 2020B02), JSPS KAKENHI (grant numbers JP21K16118 and JP21K08194), the Smoking Research Foundation (2021Y007), the Takeda Science Foundation, the Uehara Memorial Foundation, the MSD Life Science Foundation, the Japanese Respiratory Society Boehringer Ingelheim Research Grant Program, the Foundation of Kinoshita Memorial Enterprise, the Senri Life Science Foundation, and the Inamori Foundation.

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Authors and Affiliations

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

    Hiroshi Nabeshima & Kiyoharu Fukushima

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

    Takayuki Niitsu, Kiyoharu Fukushima & Hiroshi Kida

  3. Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan

    Kiyoharu Fukushima

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

    Kiyoharu Fukushima & Hiroshi Kida

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

    Kiyoharu Fukushima

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  1. Hiroshi Nabeshima
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  2. Takayuki Niitsu
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Correspondence to Hiroshi Kida.

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Nabeshima, H., Niitsu, T., Fukushima, K. et al. Invariant natural killer T cells and iron metabolism orchestrate skin development and homeostasis. Cell Mol Immunol (2023). https://doi.org/10.1038/s41423-023-01016-x

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  • DOI: https://doi.org/10.1038/s41423-023-01016-x

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