Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

IL-17-secreting γδ T-cell-driven Siglec-F+ neutrophils mediate lung pathology in emphysema

Cellular & Molecular Immunology volume 22, pages 1123–1125 (2025)Cite this article

Subjects

The Original Article was published on 03 June 2025

IL-17 has a well-established role in protection against fungal and bacterial infection through the recruitment and activation of neutrophils, but also plays a pathogenic role in many chronic inflammatory and autoimmune diseases through the production of inflammatory mediators [1]. While conventional αβ T cells are the primary producers of IL-17, γδ T cells activated by cytokines without T-cell receptor engagement are also a major source of IL-17 in many inflammatory disease settings. Hong et al. [2] reported that IL-17-producing γδ T cells (γδT17 cells) play a key role in the pathology of elastase-induced emphysema in mice through the recruitment and expansion of a population of highly activated neutrophils that express Siglec-F, a marker also expressed by eosinophils and alveolar macrophages.

Emphysema is a pathological subtype of chronic obstructive pulmonary disease (COPD), a chronic lung disease characterized by chronic inflammation, mucus hypersecretion, and destruction of the alveoli in the lungs, leading to breathing difficulties. Lung inflammation in COPD is commonly triggered by the inhalation of noxious particles such as cigarette smoke and can be exacerbated by viral and bacterial infection. Neutrophils and macrophages, through the release of elastase and matrix metalloproteinases, are major contributors to lung inflammation and tissue destruction in COPD. The inflammatory cytokine IL-17 plays a major role in neutrophil recruitment, and there is growing evidence of a role for IL-17 in COPD. Clinical studies have revealed elevated concentrations of IL-17A and increased numbers of CD4+T cells that secrete IL-17A and IL-17F (Th17 cells) in the blood, sputum, or lung biopsies of COPD patients [3]. Studies in a mouse model of elastase-induced emphysema demonstrated that Th17 cells were expanded in the lungs after elastase treatment and that mice deficient in IL-17 (il17-/- mice) had reduced neutrophil recruitment and emphysematous changes in the lung tissue [4]. Furthermore, mice lacking IL-23, a key driver of Th17 cells, had reduced Th17 cells and neutrophil recruitment and attenuated pulmonary inflammation and emphysema [5].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol. 2023;23:38–54.

    Article  CAS  PubMed  Google Scholar 

  2. Hong J, Kang MH, Lee J, Cha MS, Bae YS, Kim HY, et al. γδ(+) T-cell-derived IL-17A stimulates airway epithelial/stromal cells to secrete G-CSF, promoting lung-specific pathogenic Siglec-F(+) neutrophil development in PPE-induced emphysema. Cell Mol Immunol. 2025;22:791–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Le Rouzic O, Pichavant M, Frealle E, Guillon A, Si-Tahar M, Gosset P. Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations. Eur Respir J. 2017;50:1602434.

    Article  PubMed  Google Scholar 

  4. Kurimoto E, Miyahara N, Kanehiro A, Waseda K, Taniguchi A, Ikeda G, et al. IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice. Respir Res. 2013;14:5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fujii U, Miyahara N, Taniguchi A, Waseda K, Morichika D, Kurimoto E, et al. IL-23 Is essential for the development of elastase-induced pulmonary inflammation and emphysema. Am J Respir Cell Mol Biol. 2016;55:697–707.

    Article  CAS  PubMed  Google Scholar 

  6. Matsui M, Nagakubo D, Satooka H, Hirata T. A novel Siglec-F(+) neutrophil subset in the mouse nasal mucosa exhibits an activated phenotype and is increased in an allergic rhinitis model. Biochem Biophys Res Commun. 2020;526:599–606.

    Article  CAS  PubMed  Google Scholar 

  7. Borkner L, Curham LM, Wilk MM, Moran B, Mills KHG. IL-17 mediates protective immunity against nasal infection with Bordetella pertussis by mobilizing neutrophils, especially Siglec-F(+) neutrophils. Mucosal Immunol. 2021;14:1183–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. McGinley AM, Sutton CE, Edwards SC, Leane CM, DeCourcey J, Teijeiro A, et al. Interleukin-17A serves a priming role in autoimmunity by recruiting IL-1β-producing myeloid cells that promote pathogenic T Cells. Immunity. 2020;52:342–.e346.

    Article  CAS  PubMed  Google Scholar 

  9. Fukuzaki S, Righetti RF, Santos TMD, Camargo LDN, Aristóteles L, Souza FCR, et al. Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice. Am J Physiol Cell Physiol. 2021;320:C341–c354.

    Article  CAS  PubMed  Google Scholar 

  10. Voss M, Wolf L, Kamyschnikow A, Wonnenberg B, Honecker A, Herr C, et al. Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema. Am J Physiol Lung Cell Mol Physiol. 2015;309:L188–195.

    Article  CAS  PubMed  Google Scholar 

  11. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al. A randomized, Placebo-controlled Phase 2 Trial of CNTO 6785 in chronic obstructive pulmonary disease. Copd. 2017;14:476–83.

    Article  PubMed  Google Scholar 

  12. Gamell C, Bankovacki A, Scalzo-Inguanti K, Sedgmen B, Alhamdoosh M, Gail E, et al. CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa. Br J Dermatol. 2023;188:636–48.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Kingston Mills is funded by Research Ireland (Grants 22/FFP-A/10297 and 23/ARC/11991).

Author information

Authors and Affiliations

  1. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland

    Kingston H. G. Mills

Authors
  1. Kingston H. G. Mills
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Kingston H. G. Mills.

Ethics declarations

Competing interests

Kingston Mills is a cofounder and shareholder in a biotech start-up company that is involved in the development of anti-inflammatory therapeutics.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mills, K.H.G. IL-17-secreting γδ T-cell-driven Siglec-F+ neutrophils mediate lung pathology in emphysema. Cell Mol Immunol 22, 1123–1125 (2025). https://doi.org/10.1038/s41423-025-01322-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41423-025-01322-6

Search

Advanced search

Quick links