title: Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis.
abstract: OBJECTIVE
  Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens.
  
  
  METHODS
  Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage⁻ and Lineage⁺ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage⁻ and Lineage⁺ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit.
  
  
  RESULTS
  The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage⁻ cells compared to Lineage⁺ cells.
  
  
  CONCLUSIONS
  AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery and Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.|Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.|Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery and Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.|Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Erzhong
authors.initials: E
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery and Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.|Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Crombruggen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery and Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.|Beijing Key Laboratory of Nasal diseases, Beijing Institute of Otolaryngology, Beijing 100005, China. dr.luozhang@139.com.
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
keywords: IL-25; IL-33; ILC2; allergic rhinitis; group 2 innate lymphoid cell