De Corso Eugenio, Hellings Peter W, Fokkens Wytske J, Klimek Ludger, Peters Anju T, Scadding Glenis K, Desrosiers Martin, Lee Stella E, Mullol Joaquim
UOC Otorinolaringoiatria, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.Go F.Vito 1, Roma, Italy.
The European Forum for Research and Education in Allergy and Airway Diseases Scientific Expert Team Members, Brussels, Belgium.
Curr Allergy Asthma Rep. 2024 Dec 5;25(1):7. doi: 10.1007/s11882-024-01186-2.
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.
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.
胸腺基质淋巴细胞生成素（TSLP）在各种上皮驱动的慢性炎症性疾病发病机制中的关键作用日益受到认可。本综述梳理了关于TSLP的现有证据，特别关注哮喘，然后深入探讨目前对其在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）中作用的理解。我们探讨TSLP在哮喘和CRSwNP发病机制中的作用，这两种情况通常相互关联，统称为“全球气道疾病”。此外，本综述评估了抑制TSLP作为CRSwNP和哮喘治疗选择的治疗潜力。进行了系统的文献检索；所选出版物用于描述TSLP的生物学特性，包括其表达以及对炎症的多种影响。
TSLP在哮喘中的作用已得到充分证实，tezepelumab（首个被批准用于治疗2型（T2）高和T2低的重度哮喘的抗TSLP单克隆抗体）的疗效也支持了这一点。基因和机制研究表明TSLP可调节T2炎症并影响非T2反应，这证明TSLP可能是CRSwNP发病机制的关键因素。NAVIGATOR试验的初步数据表明，tezepelumab可能减轻合并哮喘患者的CRSwNP症状。虽然需要进一步研究以阐明TSLP在CRSwNP中的作用程度，但本综述强调了抗TSLP疗法作为治疗重度、难治性CRSwNP新方法的潜力。如果这些初步发现得到证实，靶向TSLP可能成为治疗伴或不伴合并哮喘的CRSwNP的有前景策略。
