Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that
affects one in ten people. Patients suffering from severe AD eventually progress to
develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling
between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin
(TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial
cells directly communicate to cutaneous sensory neurons via TSLP to promote itch.
We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of
TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then
acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch
behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes
activates both primary afferent neurons and immune cells to promote inflammatory responses
in the skin and airways.
Copyright © 2013 Elsevier Inc. All rights reserved.