Important Work: Dendritic epidermal T cells regulate skin antimicrobial barrier function

This from the Scripps Research Institute published in the Journal of Clinical Investigation

JCI – Dendritic epidermal T cells regulate skin antimicrobial barrier function:

Research Article

Dendritic epidermal T cells regulate skin antimicrobial barrier function

Amanda S. MacLeod1, Saskia Hemmers1,2, Olivia Garijo1, Marianne Chabod1, Kerri Mowen1,2, Deborah A. Witherden1 andWendy L. Havran1
1Department of Immunology and Microbial Science and
2Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.
Address correspondence to: Wendy L. Havran, The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 N. Torrey Pines Road, IMM-8, La Jolla, California 92037, USA. Phone: 858.784.2742; Fax: 858.784.8179; E-mail: havran@scripps.edu.
Published September 24, 2013
Received for publication March 21, 2013, and accepted in revised form August 1, 2013.

The epidermis, the outer layer of the skin, forms a physical and antimicrobial shield to protect the body from environmental threats. Skin injury severely compromises the epidermal barrier and requires immediate repair. Dendritic epidermal T cells (DETC) reside in the murine epidermis where they sense skin injury and serve as regulators and orchestrators of immune responses. Here, we determined that TCR stimulation and skin injury induces IL-17A production by a subset of DETC. This subset of IL-17A–producing DETC was distinct from IFN-γ producers, despite similar surface marker profiles. Functionally, blocking IL-17A or genetic deletion of IL-17A resulted in delayed wound closure in animals. Skin organ cultures from Tcrd–/–, which lack DETC, and Il17a–/– mice both exhibited wound-healing defects. Wound healing was fully restored by the addition of WT DETC, but only partially restored by IL-17A–deficient DETC, demonstrating the importance of IL-17A to wound healing. Following skin injury, DETC-derived IL-17A induced expression of multiple host-defense molecules in epidermal keratinocytes to promote healing. Together, these data provide a mechanistic link between IL-17A production by DETC, host-defense, and wound-healing responses in the skin. These findings establish a critical and unique role of IL-17A–producing DETC in epidermal barrier function and wound healing.

David G. Armstrong

Dedicated to amputation prevention, wound healing, diabetic foot, biotechnology and the intersection between medical devices and consumer electronics.

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