| Autor: |
Brüggemann TR; Pulmonary and Critical Care Medicine, Department of Internal Medicine., Peh HY; Pulmonary and Critical Care Medicine, Department of Internal Medicine., Tavares LP; Pulmonary and Critical Care Medicine, Department of Internal Medicine., Nijmeh J; Pulmonary and Critical Care Medicine, Department of Internal Medicine., Shay AE; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, and., Rezende RM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Lanser TB; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Serhan CN; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, and., Levy BD; Pulmonary and Critical Care Medicine, Department of Internal Medicine. |
| Abstrakt: |
Eosinophils (Eos) reside in multiple organs during homeostasis and respond rapidly to an inflammatory challenge. Although Eos share chemical staining properties, they also demonstrate phenotypic and functional plasticity that is not fully understood. Here, we used a murine model of allergic lung inflammation to characterize Eos subsets and determine their spatiotemporal and functional regulation during inflammation and its resolution in response to resolvin D2 (RvD2), a potent specialized proresolving mediator. Two Eos subsets were identified by CD101 expression with distinct anatomic localization and transcriptional signatures at baseline and during inflammation. CD101 low Eos were predominantly located in a lung vascular niche and responded to allergen challenge by moving into the lung interstitium. CD101 high Eos were predominantly located in bronchoalveolar lavage (BAL) and extravascular lung, only present during inflammation, and had transcriptional evidence for cell activation. RvD2 reduced total Eos numbers and changed their phenotype and activation by at least two distinct mechanisms: decreasing interleukin 5-dependent recruitment of CD101 low Eos and decreasing conversion of CD101 low Eos to CD101 high Eos. Collectively, these findings indicate that Eos are a heterogeneous pool of cells with distinct activation states and spatiotemporal regulation during resolution of inflammation and that RvD2 is a potent proresolving mediator for Eos recruitment and activation. |
