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. 2018 Jul 13;9:1595. doi: 10.3389/fimmu.2018.01595

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Copyright © 2018 Varricchi, Pecoraro, Marone, Criscuolo, Spadaro, Genovese and Marone.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic representation of the production of thymic stromal lymphopoietin (TSLP) and its signaling complex via a cooperative stepwise mechanism on the surface of cellular targets. A plethora of triggers including allergens, cigarette smoke extracts, cytokines, viral, bacterial and fungal products, and tryptase can activate lung and gut epithelial cells and keratinocytes to release TSLP. The latter, which is positively charged, binds to thymic stromal lymphopoietin receptor (TSLPR), which is negatively charged, with high affinity and fast kinetics. Then, IL-7Rα associates with performed TSLPR:TSLP binary complex to form the ternary TSLPR-TSLP-IL-7Rα complex (44). This receptor complex on cells co-expressing TSLPR and IL-7Rα phosphorylates JAK and STAT5 to initiate proinflammatory signaling.