TSLP and IL-33 Reciprocally Regulate Each Other’s Lung Protein Expression and Receptor Expression on ILC2 following Aeroallergen Challenge in Mice.
Friday, March 2, 2018: 2:00 PM
S210C (Convention Center)
Shinji Toki, PhD, ,

The epithelial cell-derived danger signal mediators, TSLP and IL-33 are consistently associated with adaptive Th2 immune responses. TSLP and IL-33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanisms regulating the synergism by which TSLP and IL-33 regulate the synergistic activation of ILC2 are unknown.


BALB/c background WT mice pre-administered with recombinant TSLP (rTSLP) or vehicle, TSLP receptor (TSLPR) deficient mice, and IL-33 receptor (ST2) deficient mice were challenged intranasally with Alternaria-extract or vehicle. BALF and lungs were harvested to detect IL-33 release (1 hr after challenge) and TSLP protein expression (6 hr after challenge) by ELISA. Whole lung cells from WT mice challenged intranasally with rTSLP or rIL-33, and isolated lung ILC2 stimulated with rTSLP or rIL-33 in vitro were used to measure TSLPR and ST2 expression on ILC2 by flow cytometry.


rTSLP pre-administration increased Alternaria-induced IL-33 release into BALF, and TSLPR deficiency decreased the Alternaria-induced IL-33 release. ST2 deficiency decreased Alternaria-induced TSLP expression in the lung. Further, rTSLP administration increased ST2 expression, and rIL-33 administration increased TSLPR expression on lung ILC2 in vivo and in vitro.


TSLP and IL-33 reciprocally increased each other’s protein expression or release in the lung, and each other’s receptor expression on lung ILC2. This may be one mechanism by which TSLP and IL-33 synergistically activate ILC2 and augment ILC2-mediated allergic airway inflammation.