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Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis

Authors :
Carolyn M Walsh
Rose Z Hill
Jamie Schwendinger-Schreck
Jacques Deguine
Emily C Brock
Natalie Kucirek
Ziad Rifi
Jessica Wei
Karsten Gronert
Rachel B Brem
Gregory M Barton
Diana M Bautista
Source :
eLife, Vol 8 (2019)
Publication Year :
2019
Publisher :
eLife Sciences Publications Ltd, 2019.

Abstract

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch.

Details

Language :
English
ISSN :
2050084X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.0278c3cd974b42de9fff49837b00bc9c
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.48448