Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation

Abstract

Purpose of review: Allergic diseases are thought to be driven by aberrant immune responses. Epithelium responds to various environmental factors by releasing key cytokines, such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25. Although there are important differences among these cytokines, there are also similarities which confound a clear understanding of the exact roles of these cytokines. The purpose of this review is to analyze the advances in biology and functions of these cytokines over recent years, elucidate their differences and similarities, and provide new conceptual understanding as to their roles in allergic diseases.

Recent findings: There are distinct differences in the timing, onset, and kinetics of the responses and perhaps in the potency of action of TSLP, IL-33, and IL-25. Newer roles of these cytokines have been described, including airway remodeling and fibrosis-related functions (TSLP, IL-33, and IL-25), fetal-maternal interface (IL-33 and TSLP), T-cell biology (TSLP), group 2 innate lymphoid cell biology (TSLP, IL-33, and IL-25), and mast cell-neutrophil axis (IL-33). Novel roles of these cytokines in the pathogenesis of atopic dermatitis and asthma have also been described.

Summary: TSLP, IL-25, and IL-33 are increasingly recognized to play important roles in the pathophysiology of allergic diseases. More clear recognition of the differences and similarities of the immunological pathways mediated by these cytokines would help optimize the treatment for allergic diseases.

Figure 1

Concepts influencing IL-33, TSLP and IL-25 biology are depicted as nodes. Distinct shapes are assigned to a unique biological concept with rhomboid (disease state), rounded squares (biological process), octagon (cell or tissue) and ellipse (factor such as cytokine or allergen). Network was generated using Cytoscape (http://www.cytoscape.org/ v3.1.1). Force directed algorithm was applied which pulls connected nodes together and pushes disconnected nodes apart. Modules are identified based on emergent patterns and domain knowledge.