Carla Winkler1, Thomas Hochdörfer2, Elisabeth Israelsson2, Annemarie Hasselberg2, Anders Cavallin2, Kristofer Thörn2, Daniel Muthas2, Shervin Shojaee3, Katrin Lüer4, Meike Müller4, Jenny Mjösberg5, Outi Vaarala2, Jens Hohlfeld6, Katerina Pardali2. 1. Respiratory, Inflammation and Autoimmunity, Biotech IMED Unit, AstraZeneca, Gothenburg, Sweden. Electronic address: carla.winkler@astrazeneca.com. 2. Respiratory, Inflammation and Autoimmunity, Biotech IMED Unit, AstraZeneca, Gothenburg, Sweden. 3. Discovery Science, Biotech IMED Unit, AstraZeneca, Gothenburg, Sweden. 4. Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. 5. Center for Infectious Diseases, Karolinska Institute, Stockholm, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 6. Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany; Member of the German Center for Lung Research (BREATH), Hannover, Germany; Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
Abstract
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune responses. ILC2 numbers are increased in asthmatic patients compared with healthy control subjects. Thus far, human data describing their phenotype during acute allergic inflammation in the lung are incomplete. OBJECTIVES: This study aims to characterize and compare blood- and lung-derived ILC2s before and after segmental allergen challenge in patients with mild-to-moderate asthma with high blood eosinophil counts (≥300 cells/μL). METHODS: ILC2s were isolated from blood and bronchoalveolar lavage (BAL) fluid before and after segmental allergen challenge. Cells were sorted by means of flow cytometry, cultured and analyzed for cytokine release or migration, and sequenced for RNA expression. RESULTS: ILC2s were nearly absent in the alveolar space under baseline conditions, but numbers increased significantly after allergen challenge (P < .05), whereas at the same time, ILC2 numbers in blood were reduced (P < .05). Prostaglandin D2 and CXCL12 levels in BAL fluid correlated with decreased ILC2 numbers in blood (P = .004, respective P = .024). After allergen challenge, several genes promoting type 2 inflammation were expressed at greater levels in BAL fluid compared with blood ILC2s, whereas blood ILC2s remain unactivated. CONCLUSION: ILC2s accumulate at the site of allergic inflammation and are recruited from the blood. Their transcriptional and functional activation pattern promotes type 2 inflammation.
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune responses. ILC2 numbers are increased in asthmatic patients compared with healthy control subjects. Thus far, human data describing their phenotype during acute allergic inflammation in the lung are incomplete. OBJECTIVES: This study aims to characterize and compare blood- and lung-derived ILC2s before and after segmental allergen challenge in patients with mild-to-moderate asthma with high blood eosinophil counts (≥300 cells/μL). METHODS: ILC2s were isolated from blood and bronchoalveolar lavage (BAL) fluid before and after segmental allergen challenge. Cells were sorted by means of flow cytometry, cultured and analyzed for cytokine release or migration, and sequenced for RNA expression. RESULTS: ILC2s were nearly absent in the alveolar space under baseline conditions, but numbers increased significantly after allergen challenge (P < .05), whereas at the same time, ILC2 numbers in blood were reduced (P < .05). Prostaglandin D2 and CXCL12 levels in BAL fluid correlated with decreased ILC2 numbers in blood (P = .004, respective P = .024). After allergen challenge, several genes promoting type 2 inflammation were expressed at greater levels in BAL fluid compared with blood ILC2s, whereas blood ILC2s remain unactivated. CONCLUSION: ILC2s accumulate at the site of allergic inflammation and are recruited from the blood. Their transcriptional and functional activation pattern promotes type 2 inflammation.
Authors: Maya E Kotas; Jérémie Dion; Steven Van Dyken; Roberto R Ricardo-Gonzalez; Claire J Danel; Camille Taillé; Luc Mouthon; Richard M Locksley; Benjamin Terrier Journal: JCI Insight Date: 2021-06-22