| First Author | Kotas ME | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 12 | PubMed ID | 33974563 |
| Mgi Jnum | J:322059 | Mgi Id | MGI:6751009 |
| Doi | 10.1172/jci.insight.143366 | Citation | Kotas ME, et al. (2021) A role for IL-33-activated ILC2s in eosinophilic vasculitis. JCI Insight 6(12) |
| abstractText | Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Ralpha. In the absence of IL4Ralpha or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Ralpha signaling may be potential targets for further study and therapeutic targeting in patients with EGPA. |
