Arch Bronconeumol. 2017;53(10):545–546 www.archbronconeumol.org Editorial Thymic Stromal Lymphopoietin: A Promising Target in the Treatment of Asthma? Linfopoyetina del estroma tímico: ¿un objetivo prometedor para el tratamiento del asma? I˜ nigo Ojanguren a,b , James G. Martin c , Catherine Lemiere a,* a Centre intégré universitaire de santé et des services sociaux du Nord-de-l’Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Université de Montréal, Montréal, Quebec, Canada b CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Barcelona, Spain c Meakins Christie Laboratories, Department of Medicine, McGill University, Research Institute of the McGill University Health Center, Canada Thymic stromal lymphopoietin (TSLP) In the last decade, it has become clear that asthma is a heteroge- neous disease composed of several phenotypes. The identification of those phenotypes has been associated with the development of biological therapies targeting antibodies, cytokines and their recep- tors such as immunoglobulin E, interleukin (IL)-5 and IL-5 receptor, or IL-13 in the treatment of severe asthma. Thymic stromal lymphopoietin (TSLP) is an epithelial derived cytokine that belongs to the type I cytokine group, which is part of the IL-2 cytokine family (IL-2, IL-4, IL-7, IL-9, IL-13, IL-21). 1 TSLP was first discovered in 1994 in the supernatants of a murine thymic stromal cell line that supported the growth of a pre-B cell line. In the year 2000, a TSLP human homolog was isolated. The human TSLP gene is located on chromosome 5q22.1 next to the atopic cytokine cluster (IL-4 IL-5, IL-9, IL-13) of the chromosome 5q31. Its important role in allergic airway inflammation has become evi- dent over the past few years. 1 Polymorphisms of the TSLP gene have been shown to be associated with allergic asthma. There is a wide spectrum of stimuli that are able to trigger TSLP activation; for example, viral infections, bacterial peptidoglycan, air pollutants, and allergens. 2 TSLP acts by binding to its receptor (TSLP-R), which consists of a TSLP-binding  chain and an IL-7R chain. 3 TSLP is expressed through injured epithelial cells of the skin, abdomen, and lungs. It exerts its main biological actions on dendritic cells (DCs) and mast cells. 4 TSLP is also involved in the Th2 differentiation of T lymphocytes. 5 There is evidence that basophils, eosinophils, and airway smooth muscle cells express TSLP-Rs and thus, TSLP could enable them to release Th2 cytokines. 6 * Corresponding author. E-mail address: catherine.lemiere@umontreal.ca (C. Lemiere). Role of TSLP in the Type 2 response The principal role of TSLP is to induce a Th2 adaptive response by means of diverse cells. Dendritic cells play an important role in the process of inducing this Th2 response. When DCs are stimu- lated by TSLP, an upregulation of the ligand OX40L expressed on DCs occurs, which promotes the transformation of CD4 + cells into activated Th2 cells. 3 TSLP also stimulates mast cells to release Th2 inflammatory cytokines such as IL-4, IL-5, IL-6, and IL-13. Under resting conditions, CD4 + and CD8 + T-cells are insensitive to TSLP. However, the number of TSLP receptors increases on the surface of CD4 + and CD8 + T cells after their activation. Following a T-cell receptor stimulation, TSLP can promote CD4 + and CD8 + T-cell pro- liferation through the induction of the IL-4 gene transcription. 3 The role of TSLP in B-cells during an allergic inflammatory reaction has not been described. TSLP can also activate innate lymphoid cells (ILCs) in an allergen- independent manner. Activated ILCs produce high amounts of IL-5 and IL-13, and can induce eosinophilic airway inflammation inde- pendently of T-cells. 3 Insults to the airway epithelium such as oxidants (ozone and other irritants) may lead to activation of these cells, contributing to airway hyperresponsiveness that is indepen- dent of adaptive immunity. 7 Role of TSLP in asthma There is evidence that TSLP plays an important role in induc- ing an allergic asthmatic response in not only transgenic asthmatic mice models, but also in humans. Several studies have demon- strated a relationship between the expression of TLSP, airway hyperresponsiveness, and airflow limitation. 8 In 2014, Gauvreau et al. 9 conducted a double-blind, placebo-controlled study, in which 31 patients with mild allergic asthma were randomized to receive three monthly doses of an intravenous anti-TSLP monoclonal immunoglobulin or placebo. Allergen challenges were conducted on day 42 and day 84 to assess the effect of the anti-TSLP on FEV 1 during the asthmatic reaction. The maximum percentage http://dx.doi.org/10.1016/j.arbres.2017.05.015 0300-2896/© 2017 SEPAR. Published by Elsevier Espa ˜ na, S.L.U. All rights reserved. 1579-2129