iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata

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

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.

Keywords: Alopecia areata; Animal model; IL-10; iNKT10; α-GalCer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alopecia Areata / immunology*
  • Animals
  • Autoimmunity
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Galactosylceramides / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / transplantation
  • Skin / pathology*
  • Skin Transplantation*
  • Transplantation, Heterologous

Substances

  • Galactosylceramides
  • Interleukin-2
  • alpha-galactosylceramide
  • Interleukin-10