COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease.
العنوان: | COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease. |
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المؤلفون: | Flayer CH, Linderholm AL, Ge MQ, Juarez M, Franzi L, Tham T, Teuber M, Liao SY, Schivo M, Kuhn B, Zeki A, Haczku A |
المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Apr 03. Date of Electronic Publication: 2024 Apr 03. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
مستخلص: | Rationale: Pulmonary innate immune cells play a central role in the initiation and perpetuation of chronic obstructive pulmonary disease (COPD), however the precise mechanisms that orchestrate the development and severity of COPD are poorly understood. Objectives: We hypothesized that the recently described family of innate lymphoid cells (ILCs) play an important role in COPD. Methods: Subjects with COPD and healthy controls were clinically evaluated, and their sputum samples were assessed by flow cytometry. A mouse model of spontaneous COPD [genetically deficient in surfactant protein-D (SP-D -/- )] and ozone (O Measurements and Main Results: COPD was characterized by poor spirometry, sputum inflammation, and the emergence of sputum GATA3 + ILCs (ILC2s), but not T-bet + ILCs (ILC1s) nor RORγt + ILCs (ILC3s). COPD subjects with elevated sputum ILC2s (the ILC2 high group) had worse spirometry and sputum neutrophilia and eosinophilia than healthy and ILC2 low subjects. This was associated with the presence of dual-positive IL-5 + IL-17A + and IL-13 + IL-17A + ILCs and nonfunctional SP-D in the sputum in ILC2 high subjects. SP-D -/- mice showed spontaneous airway neutrophilia. Lack of SP-D in the mouse lung licensed ILC2s to produce IL-17A, which was dose-dependently inhibited by recombinant SP-D. SP-D -/- mice showed enhanced susceptibility to O Conclusions: We report that the presence of sputum ILC2s predicts the severity of COPD, and unravel a novel pathway of IL-17A plasticity in lung ILC2s, prevented by the immunomodulatory protein SP-D. |
معلومات مُعتمدة: | R01 HL148715 United States HL NHLBI NIH HHS |
تواريخ الأحداث: | Date Created: 20231204 Latest Revision: 20240411 |
رمز التحديث: | 20240411 |
مُعرف محوري في PubMed: | PMC10690341 |
DOI: | 10.1101/2023.11.21.23298837 |
PMID: | 38045302 |
قاعدة البيانات: | MEDLINE |
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