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Elife. 2019 Oct 21;8. pii: e48448. doi: 10.7554/eLife.48448.

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

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
2
Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, United States.
3
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, United States.
4
Buck Institute for Research on Aging, Novato, United States.
5
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States.
#
Contributed equally

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.

KEYWORDS:

atopic dermatitis; chronic itch; immunology; inflammation; itch; mouse; neuroimmune; neuroscience; neutrophils; somatosensory

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