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

2 Citations (Scopus)

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

Fingerprint

Alopecia Areata
Natural Killer T-Cells
Autoimmunity
T-Lymphocytes
Interleukin-10
Hair
Autoimmune Diseases
Galactosylceramides
Intradermal Injections
Skin
SCID Mice
Scalp
Interleukin-2
Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

iNKT cells ameliorate human autoimmunity : Lessons from alopecia areata. / Ghraieb, Amal; Keren, Aviad; Ginzburg, Alex; Ullmann, Yehuda; Schrum, Adam G.; Paus, Ralf; Gilhar, Amos.

In: Journal of Autoimmunity, Vol. 91, 01.07.2018, p. 61-72.

Research output: Contribution to journalArticle

Ghraieb, A, Keren, A, Ginzburg, A, Ullmann, Y, Schrum, AG, Paus, R & Gilhar, A 2018, 'iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata', Journal of Autoimmunity, vol. 91, pp. 61-72. https://doi.org/10.1016/j.jaut.2018.04.001
Ghraieb, Amal ; Keren, Aviad ; Ginzburg, Alex ; Ullmann, Yehuda ; Schrum, Adam G. ; Paus, Ralf ; Gilhar, Amos. / iNKT cells ameliorate human autoimmunity : Lessons from alopecia areata. In: Journal of Autoimmunity. 2018 ; Vol. 91. pp. 61-72.
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