Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells

Abstract

The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) plays a key role in the development and progression of atopic disease and has notably been shown to directly promote the allergic inflammatory responses that characterize asthma. Current models suggest that TSLP is produced by epithelial cells in response to inflammatory stimuli and acts primarily upon dendritic cells to effect a T helper type 2-type inflammatory response. Recent reports, however, have shown that epithelial cells themselves are capable of expressing the TSLP receptor (TSLPR), and may thus directly contribute to a TSLP-dependent response. We report here that beyond simply expressing the receptor, epithelial cells are capable of dynamically regulating TSLPR in response to the same inflammatory cues that drive the production of TSLP, and that epithelial cells produce chemokine C–C motif ligand 17, a T helper type 2-associated chemokine, in response to stimulation with TSLP. These data suggest that a direct autocrine or paracrine response to TSLP by epithelial cells may initiate the initial waves of chemotaxis during an allergic inflammatory response. Intriguingly, we find that the regulation of TSLPR, unlike TSLP, is independent of nuclear factor kappa-light-chain-enhancer of activated B cells, suggesting that the cell may be able to independently regulate TSLP and TSLPR levels in order to properly modulate its response to TSLP. Finally, we show evidence for this dynamic regulation occurring following the viral infection of primary epithelial cells from asthmatic patients. Taken together, the data suggest that induction of TSLPR and a direct response to TSLP by epithelial cells may play a novel role in the development of allergic inflammation.

Keywords:

• TSLP
• TSLPR
• RSV
• asthma
• epithelium

Acknowledgments

We thank Whitney Xu and Theingi Aye for excellent technical assistance; Drs Daniel Campbell, Joan Goverman, and Daniel Bowen-Pope for critical discussion of the manuscript before submission; and members of the Ziegler laboratory for helpful discussions throughout the duration of this work. We thank Sylvia McCarty for administrative support. This work was funded in part from grants AI068731 and HL098067 to SFZ and HL102708 to SFZ and JSD.

Disclosure

The authors report no conflicts of interest in this work.