Thymic stromal lymphopoietin and allergic disease

Abstract

The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders.

Figure 1. Schematic representation of the TSLP receptor complex

Schematic of TSLP bound by the TSLP receptor. JAK1 and JAK2, as well as the STAT proteins shown to be activated following receptor engagement, are indicated. STAT5 is in bold as it is the predominant STAT protein that is activated. Listed below are some outcomes of TSLP receptor engagement.

Figure 2. TSLP target cells at mucosal surfaces

Schematic representation of TSLP activity at mucosal surfaces. A variety of stimuli are capable inducing TSLP expression by barrier epithelial cells. TSLP can then activate resident cells, especially dendritic cells, to drive a type 2 response.