Radiation-Induced Dermatitis is Mediated by IL17-Expressing γδ T Cells.
Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or upon accidental nuclear exposure. However, the pathogenic immune mechanisms underlying this injury are still poorly understood. We seek to discover how the dysregulated immune response after irradiation orchestrates skin inflammation. The skin on the left flank of C57BL/6J wild-type and C57BL/6J Tcrd-/-mice, which are deficit in γδ T cells, was exposed to a single X-ray dose of 25 Gy, and the right-flank skin was used as a sham-irradiated control. At 4 weeks postirradiation, the wild-type skin exhibited signs of depilation, erythema and desquamation. Histological analysis showed hyperproliferation of keratinocytes and acanthosis. Dramatic elevation of IL17-expressing T cells was identified from the irradiated skin, which was mainly contributed by γδ T cells and innate lymphoid cells, rather than Th17 cells. Furthermore, protein levels of critical cytokines for IL17-expressing γδ T cell activation, IL1β and IL23 were found markedly upregulated. Lastly, radiation-induced dermatitis was significantly attenuated in γδ T cell knockout mice. In vitro, normal human epidermal keratinocytes (NHEKs) could be initiator cells of inflammation by providing a great number of pro-inflammatory mediators upon radiation, and as well as effector cells of epidermal hyperplasia in response to exogenous IL17 and/or IL22 treatment. Our findings implicate a novel role of IL17-expressing γδ T cells in mediating radiation-induced skin inflammation. This study reveals the innate immune response pathway as a potential therapeutic target for radiation skin injury.
a   Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Wupeng
W
Liao
b   Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032.|c   Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032.
Tom K
TK
Hei
a   Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Simon K
SK
Cheng