iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata

作者：Ghraieb Amal; Keren Aviad; Ginzburg Alex; Ullmann Yehuda; Schrum Adam G; Paus Ralf; Gilhar Amos^*

来源：Journal of Autoimmunity, 2018, 91: 61-72.

DOI：10.1016/j.jaut.2018.04.001

• Alopecia areata
• Animal model
• iNKT10
• IL-10
• alpha-GalCer

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, alpha-galactosylceramide (alpha-GalCer), which stimulates iNKT cells to expand and produce IL-10. Moreover, in preestablished humanized mouse AA lesions, hair regrowth is promoted by alpha-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.

• 出版日期2018-7