Details

Autor(en) / Beteiligte

• Wilson, Sarah R.
• Thé, Lydia
• Batia, Lyn M.
• Beattie, Katherine
• Katibah, George E.
• McClain, Shannan P.
• Pellegrino, Maurizio
• Estandian, Daniel M.
• Bautista, Diana M.

Titel

The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch

Ist Teil von

• Cell, 2013-10, Vol.155 (2), p.285-295

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Epithelial cells communicate to sensory neurons via TSLP to promote itch•ORAI1/NFAT calcium signaling regulates release of TSLP from keratinocytes•TSLP is a robust pruritogen that promotes itch-evoked scratching•TSLP-evoked itch behaviors require TRPA1 ion channels that promote inflammation The proinflammatory cytokine TSLP is a potent driver of dermatitis and is primarily thought to act through modulation of immune cells. TSLP is now found to directly activate sensory neurons via signaling involving ORAI1 and TRPA1 channels to trigger itch behaviors.