Thymic Stromal Lymphopoietin (TSLP): Evidence in Respiratory Epithelial-driven Diseases Including Chronic Rhinosinusitis with Nasal Polyps

Purpose of the review: Thymic stromal lymphopoietin (TSLP) is increasingly recognized for its pivotal role in the pathogenesis of various epithelial-driven chronic inflammatory diseases. This review navigates the existing evidence on TSLP, with a particular focus on asthma, before delving into the current understanding of its role in chronic rhinosinusitis with nasal polyps (CRSwNP). We explore the role of TSLP in the pathogenesis of asthma and CRSwNP, two conditions often interconnected and collectively referred to as"Global Airway Disease". Additionally, this review assesses the therapeutic potential of TSLP inhibition as a treatment option for both CRSwNP and asthma. A systematic literature search was conducted; selected publications were used to describe the biology of TSLP, including its expression and diverse effects on inflammation.

Recent findings: The role of TSLP in asthma is well established and supported by the efficacy of tezepelumab, the first anti-TSLP monoclonal antibody approved for both type 2 (T2)-high and T2-low severe asthma. TSLP may be a key contributor to CRSwNP pathogenesis as evidenced by genetic and mechanistic studies in which TSLP has been shown to regulate T2 inflammation and influence non-T2 responses. Preliminary data from the NAVIGATOR trial indicate that tezepelumab may reduce CRSwNP symptoms in patients with comorbid asthma. While further research is required to clarify the extent of TSLP contribution in CRSwNP, this review highlights the potential of anti-TSLP therapies as a novel approach for managing severe, uncontrolled CRSwNP. If these preliminary findings are confirmed, targeting TSLP could become a promising strategy to treat CRSwNP with or without comorbid asthma.