Thymic stromal lymphopoietin as a therapeutic target in patients with chronic rhinosinusitis and nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa, predominantly characterized by epithelial dysfunction and chronic heterogeneous mucosal inflammation. CRSwNP and asthma are common comorbidities with overlapping pathophysiology, epithelial impairment, and activation of downstream type 2 inflammation. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that sits at the top of the immunological cascade and initiates and amplifies type 2-dependent and -independent inflammatory responses. Although the role of TSLP in asthma has been well described, the role of TSLP in CRSwNP has yet to be comprehensively outlined. This review examines the evidence for TSLP as a key factor in CRSwNP pathogenesis. We explore what is known about TSLP expression patterns within the sinonasal mucosa, finding that TSLP expression is increased in patients with CRSwNP compared with healthy patients, and in eosinophilic- versus non-eosinophilic CRSwNP. We discuss the impact of environmental triggers and genetic factors on TSLP expression and activity, as well as other upstream regulators of TSLP signaling. We then consider the known mechanisms and effects of TSLP signaling on the recruitment and activation of various immune and structural cell types in CRSwNP. Finally, we consider the available evidence on the therapeutic potential of targeting TSLP signaling for the treatment of CRSwNP and discuss ongoing trials of promising therapeutic candidates.