title: Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps.
abstract: OBJECTIVE
  Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disorder with a poorly understood pathophysiology. Recent findings show that epithelial-derived cytokines, including thymic stromal lymphopoietin, IL-33, and IL-25, can exacerbate Th2 immune responses, ultimately leading to recalcitrant chronic rhinosinusitis and nasal polyps. Although IL-25 is increased in CRSwNP, the targeting of IL-25 as a therapeutic strategy remains largely unexplored. In this review, we outline the many recent advances in our understanding of the association between IL-25 and CRSwNP.
  
  
  RESULTS
  Recently, we demonstrated that IL-25, produced primarily by sinonasal epithelial cells and infiltrating mast cells, plays an important role in the pathogenesis of CRSwNP in Asian patients. Furthermore, IL-25 and IL-25R are elevated in nasal polyps. This cytokine has roles in the pathogenesis of CRSwNP via modulating group 2 innate lymphoid cells (ILC2s). Similarly, ILC2 enrichment has been reported in CRSwNP patients, and a positive correlation has been shown between ILC2s and CRSwNP. Clinical trials blocking thymic stromal lymphopoietin and IL-33 pathways are ongoing using monoclonal antibodies, AMG157 and AMG282, against CRSwNP, respectively.
  
  
  CONCLUSIONS
  Studies on the role played by IL-25 in the pathogenesis of CRSwNP are accumulating and suggest the possibility of a novel therapeutic strategy for treating CRSwNP.
authors.affiliation: aObstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine bDepartment of Biomedical Sciences, Seoul National University College of Medicine cDepartment of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center dClinical Mucosal Immunology Study Group eDepartment of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital fIschemic/Hypoxic Disease Institute, Seoul National University College of Medicine gCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Lee
authors.forename: Dae Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Shin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D020381:Interleukin-17 / Q000276:immunology*; D058990:Molecular Targeted Therapy; D009298:Nasal Polyps / Q000276:immunology / Q000628:therapy*; D012220:Rhinitis / Q000276:immunology / Q000628:therapy*; D012852:Sinusitis / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; C486701:IL25 protein, human; D020381:Interleukin-17