title: Thymic Stromal Lymphopoietin: To Cut a Long Story Short.
abstract: Thymic stromal lymphopoietin (TSLP) was identified more than 20 years ago as a secreted factor of a mouse thymic stromal cell line; later, a human orthologue was also identified. The signaling pathway triggered by TSLP has been extensively studied, and upregulation of the cytokine itself is linked to the pathogenesis of numerous Th2-related diseases, including atopic dermatitis, asthma, allergic responses, as well as certain types of cancers. On the other hand, TSLP mediates several immune homeostatic functions in both the gut and the thymus. Thus, a paradox occurs; why is TSLP homeostatic in certain tissues and a hallmark of exacerbated Th2 responses in the aforementioned pathologies? We and others have recently shown that in humans a novel isoform exists; this is a shorter isoform of TSLP whose expression is constitutive and controlled by a separate promoter. Short TSLP isoform mediates the homeostatic functions, whereas the long isoform is expressed at low/undetectable level at steady state and upregulated during inflammation in several tissues. Here we review the most recent data concerning the differential expression of the 2 isoforms and provide a potential explanation to the paradox. TSLP is regarded as a promising target for treatment of relevant pathologies, with a number of clinical trials already underway. It is important to design new strategies aimed at leaving intact the homeostatic effects of the short isoform while targeting the inflammatory effects of the long isoform.
authors.affiliation: Vascular Pathophysiology Area, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Katerina
authors.initials: K
authors.lastname: Tsilingiri
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy and University of Milan.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fornasa
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy and University of Milan.
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
keywords: Atopic Diseases; DC, dendritic cell; Gut Homeostasis; IFN, interferon; IL, interleukin; ILC, innate lymphoid cells; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; TLR, toll-like receptor; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin protein receptor; Therapeutic Targets; Thymic Stromal Lymphopoietin; Treg, regulatory T cells