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Autoimmune disease

Getting to the root of hair loss in alopecia

Nature Reviews Drug Discovery volume 13, pages 724–725 (2014)Cite this article

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C3H/HeJ mice develop AA spontaneously and, in previous studies, a population of T cells expressing both CD8 and NKG2D type II integral membrane protein (CD8+NKG2D+ cells) was shown to infiltrate the alopecic skin of these mice. In this study, subcutaneously injecting CD8+NKG2D+ cells into C3H/HeJ mice induced AA in these animals within 14 weeks, whereas transferring CD8+NKG2D− cells had no such effect. Therefore, CD8+NKG2D+ cells are both necessary and sufficient to induce AA in mice.

Using microarray and immunofluorescence analyses, the expression of IFN response genes and of the common gamma chain (γc) cytokines interleukin-2 (IL-2) and IL-15 was found to be upregulated in alopecic skin from humans and mice. To investigate the importance of this expression profile in AA, the authors used a skin-graft model of the disease, where patches of skin from alopecic C3H/HeJ mice are transplanted onto healthy C3H/HeJ mice, which then develop AA. Systemic administration of antibodies specific for IFNγ, IL-2 or IL-15 receptor β at the time of grafting prevented the expansion of CD8+NKG2D+ cells and the development of AA in recipient mice.

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References

  1. Xing, L. et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nature Med. http://dx.doi.org/10.1038/nm.3645 (2014)

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  1. Natasha Bray
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Bray, N. Getting to the root of hair loss in alopecia. Nat Rev Drug Discov 13, 724–725 (2014). https://doi.org/10.1038/nrd4443

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