iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata

Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G. Schrum, Ralf Paus, Amos Gilhar

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalJournal of Autoimmunity
Volume91
DOIs
StatePublished - Jul 1 2018

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ghraieb, A., Keren, A., Ginzburg, A., Ullmann, Y., Schrum, A. G., Paus, R., & Gilhar, A. (2018). iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata. Journal of Autoimmunity, 91, 61-72. https://doi.org/10.1016/j.jaut.2018.04.001