INKT cells ameliorate human autoimmunity: Lessons from alopecia areata. (July 2018)

• Record Type: Journal Article
• Authors: Ghraieb, Amal; Keren, Aviad; Ginzburg, Alex; Ullmann, Yehuda; Schrum, Adam G.; Paus, Ralf; Gilhar, Amos
• Is Part Of: Journal of autoimmunity. Volume 91(2018)
• Page Start: 61
• Page End: 72
• Publication Date: 2018-07
• Subjects: Alopecia areata -- Animal model -- iNKT10 -- IL-10 -- α-GalCer; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2018.04.001
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: 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. Highlights: Significantly increased number of iNKT10 cells is observed in alopecia areata. NKT10 cells is a promising novel strategy for preventing and treating alopecia areata. Alopecia areata is prevented by administration of α-GalCer into an in vivo model.