title: Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness.
abstract: Group 2 innate lymphoid cells (ILC2s) have recently been identified in human nasal polyps, but whether numbers of ILC2s differ by polyp endotype or are influenced by corticosteroid use is unknown. Here, we show that eosinophilic nasal polyps contained double the number of ILC2s vs. non-eosinophilic polyps. Polyp ILC2s were also reduced by 50% in patients treated with systemic corticosteroids. Further, using a fungal allergen challenge mouse model, we detected greatly reduced Th2 cytokine-producing and Ki-67+ proliferating lung ILC2s in mice receiving dexamethasone. Finally, ILC2 Annexin V staining revealed extensive apoptosis after corticosteroid treatment in vivo and in vitro. Thus, ILC2s are elevated in the eosinophilic nasal polyp endotype and systemic corticosteroid treatment correlated with reduced polyp ILC2s. Finally, allergen-challenged mice showed reduced ILC2s and increased ILC2 apoptosis after corticosteroid treatment suggesting that ILC2 may be responsive to corticosteroids in eosinophilic respiratory disease.
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA; Rady's Children's Hospital of San Diego, Division of Rheumatology, Allergy and Immunology, San Diego, CA, USA.
authors.forename: Hannah H
authors.initials: HH
authors.lastname: Walford
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Lund
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Baum
authors.affiliation: Division of Allergy, Asthma and Immunology, Scripps Clinic, La Jolla, CA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: White
authors.affiliation: Division of Head and Neck Surgery, Scripps Green Hospital, La Jolla, CA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bergeron
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of California-San Diego, San Diego, CA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Husseman
authors.affiliation: Division of Surgical Pathology, Scripps Green Hospital, La Jolla, CA, USA.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Bethel
authors.affiliation: Division of Allergy, Asthma and Immunology, Scripps Clinic, La Jolla, CA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: Naseem
authors.initials: N
authors.lastname: Khorram
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.affiliation: Department of Medicine, University of California-San Diego, San Diego, CA, USA. Electronic address: tdoherty@ucsd.edu.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Doherty
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000145:classification*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009298:Nasal Polyps / Q000235:genetics / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D011241:Prednisone; D008775:Methylprednisolone
keywords: Alternaria; Chronic rhinosinusitis; Group 2 innate lymphoid cells; ILC2; Nasal polyps