Thymic stromal lymphopoietin: a new cytokine in asthma

Abstract

Airway epithelial cells provide mechanical and immune protection against pathogens and allergens. Following activation, these cells produce a wide range of cytokines including thymic stromal lymphopoietin (TSLP). Recently it was established that a high level of TSLP is associated with asthma in mice and in humans. These findings suggest that interfering with the ability of cells to respond to TSLP might prevent the development of airway inflammation. Our review presents current knowledge on mediators that induce TSLP production and on the actions of TSLP on different populations of cells that are related to airway inflammation. TSLP affects dendritic cells, T cells, NKT cells, and mast cells, indicative of the broad role of TSLP in the regulation of inflammatory/allergic processes.

Figure 1. Schematic showing TSLP and IL-7 receptors sharing IL-7Rα and IL-7, IL-2, IL-15, IL-9, IL-21, and IL-4 receptors sharing γ_c

The receptors are grouped to show TSLP on the far left, IL-7 complexes adjacent in both groups and IL-4 at the far right, as it activates Stat6. For each γ_c family cytokine receptor, Jak1 associates with the more “distinctive” type I cytokine receptor chain, whereas Jak3 associates with γ_c. TSLP, IL-2, IL-7, IL-9, and IL-15 primarily activate Stat5a and Stat5b, IL-4 primarily activates Stat6, and IL-21 primarily activates Stat3 and Stat1.

Figure 2. Schematic showing production of TSLP by epithelial cells in response to a range of stimuli

These include viruses, bacterial components such as peptidoglycan, lipoproteins, lipoteichoic acid, LPS and bacterial DNA, biochemical compounds like vitamin D and low-calcemic analogs [22], and pro-inflammatory cytokines TNFα and IL-1β. In turn, TSLP can act on cells of multiple lineages, inducing the production of cytokines and also having effects on proliferation and differentiation.