Journal
IMMUNOLOGICAL REVIEWS
Volume 226, Issue -, Pages 172-190Publisher
WILEY
DOI: 10.1111/j.1600-065X.2008.00713.x
Keywords
TSLP; IL-25; IL-33; mucosal immunity; Th2 cytokine responses
Categories
Funding
- NIH [AI61570, AI74878, F32-AI72943, F31-GM082187, T32-AI007532-08, T32-CA09140-30, T32-AI055438-06]
- Burroughs Wellcome Fund
- Crohn's and Colitis Foundation of America
- University of Pennsylvania
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There is compelling evidence that epithelial cells (ECs) at mucosal surfaces, beyond their role in creating a physical barrier, are integral components of innate and adaptive immunity. The capacity of these cells to license the functions of specific immune cell populations in the airway and gastrointestinal tract offers the prospect of novel therapeutic strategies to target multiple inflammatory diseases in which barrier immunity is dysregulated. In this review, we discuss the critical functions of EC-derived thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 in the development and regulation of T-helper 2 (Th2) cytokine-dependent immune responses. We first highlight recent data that have provided new insights into the factors that control expression of this triad of cytokines and their receptors. In addition, we review their proinflammatory and immunoregulatory functions in models of mucosal infection and inflammation. Lastly, we discuss new findings indicating that despite their diverse structural features and differential expression of their receptors, TSLP, IL-25, and IL-33 cross-regulate one another and share overlapping properties that influence Th2 cytokine-dependent responses at mucosal sites.
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