Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps.

Abstract Chronic rhinosinusitis with nasal polyps (CRSwNPs) 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 polyp. 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. 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. 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.