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 language | English (US) |
|---|---|
| Pages (from-to) | 61-72 |
| Number of pages | 12 |
| Journal | Journal of Autoimmunity |
| Volume | 91 |
| DOIs | |
| State | Published - Jul 1 2018 |
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Keywords
- Alopecia areata
- Animal model
- IL-10
- iNKT10
- α-GalCer
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - iNKT cells ameliorate human autoimmunity
T2 - Lessons from alopecia areata
AU - Ghraieb, Amal
AU - Keren, Aviad
AU - Ginzburg, Alex
AU - Ullmann, Yehuda
AU - Schrum, Adam G.
AU - Paus, Ralf
AU - Gilhar, Amos
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
KW - Alopecia areata
KW - Animal model
KW - IL-10
KW - iNKT10
KW - α-GalCer
UR - http://www.scopus.com/inward/record.url?scp=85045573769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045573769&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2018.04.001
DO - 10.1016/j.jaut.2018.04.001
M3 - Article
C2 - 29680372
AN - SCOPUS:85045573769
VL - 91
SP - 61
EP - 72
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -