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Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab

Venegas Garrido C1, Nair P1, Dávila I2,3,4, Pérez de Llano L5,6

1Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
2Servicio de Alergia, Hospital Universitario de Salamanca, Salamanca, Spain
3Departamento de Ciencias Biomédicas y del Diagnóstico, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain
4Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), Red de Enfermedades Inflamatorias (REI), Instituto de Salud Carlos III, Madrid, Spain
5Servicio de Neumología, Hospital Universitario Lucus Augusti, Lugo, Spain
6Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Facultade de Medicina e Odontoloxia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain

J Investig Allergol Clin Immunol 2024; Vol 34(5) : 293-302
doi: 10.18176/jiaci.1012

The airway epithelium is the first line of defense of the respiratory system against the external environment. It plays an active role in the initiation of immune and allergic responses against potential hazards. Among the various specialized cells and cytokines that participate in epithelium-induced responses, alarmins are particularly interesting, given their ample role in mediating T2 and non-T2 inflammatory mechanisms involved in the pathogenesis of asthma. Thymic stromal lymphopoietin (TSLP) is an alarmin with broad effects in asthma that result from its widespread action on multiple cell types, including eosinophils, mast cells, dendritic cells, and group-2 innate lymphoid cells. Its role in allergy-mediated responses, eosinophilic inflammation, airway hyperresponsiveness, mucus hyperproduction, viral tolerance, and airway remodeling is of the utmost importance, as more comprehensive asthma assessments have been developed to explore these pathogenic features. Therefore, blockade with targeting molecules, such as monoclonal antibodies, has emerged as a promising therapeutic option, particularly in patients with multiple pathogenic pathways. In this review, we examine the roles of alarmins (mainly TSLP) in the pathogenesis of asthma and clinical expression and discuss the effects of inhibiting TSLP on several inflammatory and clinical outcomes. We also review the literature supporting treatment with anti-TSLP biologics and the unanswered questions and unmet needs associated with targeting alarmins in asthma.

Key words: Severe asthma, Airway epithelium, Alarmins, TSLP, Tezepelumab, Biologicals