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J Autoimmun. 2018 Jul;91:61-72. doi: 10.1016/j.jaut.2018.04.001. Epub 2018 Apr 18.

iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata.

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Skin Research Laboratory, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel.
Departments of Molecular Microbiology & Immunology, Surgery, and Bioengineering, Schools of Medicine and Engineering, University of Missouri, Columbia, MO, USA.
Dermatology Research Centre, University of Manchester, MAHSC and NIHR Manchester Biomedical Research Centre, Manchester, UK; Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Skin Research Laboratory, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel. Electronic address:


Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10. Moreover, in pre-established humanized mouse AA lesions, hair regrowth is promoted by α-GalCer treatment through a process requiring both effector-memory iNKT cells, which can interact directly with CD8+/NKG2D+ T cells, and IL-10. This provides the first in vivo evidence in a humanized model of autoimmune disease that iNKT10 cells are key disease-protective lymphocytes. Since these regulatory NKT cells can both prevent the development of AA lesions and promote hair re-growth in established AA lesions, targeting iNKT10 cells may have preventive and therapeutic potential also in other autoimmune disorders related to AA.


Alopecia areata; Animal model; IL-10; iNKT10; α-GalCer


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