أعرض في EDS

COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease.

التفاصيل البيبلوغرافية
العنوان:	COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease.
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 3 ) exposure were used to examine the mechanism by which lack of functional SP-D may skew ILC2s to produce IL-17A in combination with IL-5 and IL-13, leading to a mixed inflammatory profile and more severe disease. 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 3 -induced airway neutrophilia, which was associated with the emergence of inflammatory IL-13 ⁺ IL-17A ⁺ ILCs. 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

الوصف
DOI:	10.1101/2023.11.21.23298837