Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

Dong, C; Lu, B; Zhong, C; Ou, C; Yang, X; Wang, L; Zuo, X; Xue, L; Lu, C; Wang, S; Wen, J; Ma, J; Deng, Z; Liu, Y; Ma, L; Liu, M; Lew, AM; Mukherjee, M; Nair, P; Zhong, N; Chen, R; Chen, Z; Zhang, Y; Zhang, Q

Author(s): Dong, C; Lu, B; Zhong, C; Ou, C; Yang, X; Wang, L; Zuo, X; Xue, L; Lu, C; Wang, S; Wen, J; Ma, J; Deng, Z; Liu, Y; Ma, L; Liu, M; Lew, AM; Mukherjee, M; Nair, P; Zhong, N; Chen, R; Chen, Z; Zhang, Y; Zhang, Q;
Details: Publication Year 2026-01-07,Volume 17,Issue #1,Page 1346
Journal Title: Nature Communications
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) and severe eosinophilic asthma (SEA) share a Type 2 (T2) inflammatory signature but exhibit distinct pathophysiology. We hypothesized that EGPA involves additional inflammatory mechanisms, beyond T2 immunity, that drive its systemic manifestations and treatment resistance. Using single-cell RNA sequencing, we identify interferon (IFN-I)-driven inflammation in EGPA, in contrast to TNF predominant pathway activation in SEA. IL1B(+)MX1(+) neutrophils in EGPA express IFN-stimulated genes and promote tertiary lymphoid structure formation with autoantibody production. In addition, other IFN-activated granulocytes, including APOC1(+) eosinophils, SCN7A(+) mast cells, and basophils, further contribute to immune dysregulation in EGPA, unlike TNF activated granulocytes in SEA. Longitudinal single-cell analysis of EGPA reveals an IGF1(+) macrophage population linked to EGPA relapse. In animal models of both conditions, IGF1 blockade attenuates T2 inflammation, mucin production, and goblet cell hyperplasia, highlighting IGF1 as a possible therapeutic target in T2 inflammation disease.
Publisher: Springer Nature
Keywords: *Insulin-Like Growth Factor I/metabolism/genetics/immunology/antagonists &; inhibitors; Animals; *Granulomatosis with Polyangiitis/immunology/drug therapy/genetics/pathology; Mice; Humans; Eosinophils/immunology/metabolism; Asthma/immunology/genetics/pathology; Male; Female; Macrophages/immunology/metabolism; Disease Models, Animal; Neutrophils/immunology/metabolism; Inflammation/immunology; Single-Cell Analysis; Mast Cells/immunology; Mice, Inbred C57BL
Research Division(s): Immunology
PubMed ID: 41501017
Publisher's Version: https://doi.org/10.1038/s41467-025-68104-6
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-025-68104-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-29 02:00:42

Last Modified: 2026-02-09 09:25:53