| 描述信息 |
Churg-Strauss syndrome, now known as eosinophilic granulomatosis with polyangiitis (EGPA), is a life-threatening vasculitis that is often misdiagnosed as asthma in its early stages, and its pathogenesis has not been fully elucidated. We performed scRNA-seq comparing blood, bronchoalveolar lavage fluid (BALF) and bronchi biopsies from control, asthma and EGPA subjects. We discover that an inflammatory neutrophil subset, which highly expresses interferon stimulated genes, IL1B and TNFSF13B (BAFF), is enriched in bronchi biopsies in EGPA. This corresponded with increased FCRL4+ memory B cells and anti-neutrophil autoantibodies in the patients. In pre-clinical murine models, we show that blocking IGF-1 suppressed eosinophil infiltration and ameliorated asthma and EGPA severities. In summary, we identify pathogenic mechanisms and suggest that IGF-1 is a candidate therapeutic target for Asthma and EGPA. |
