IL-23 antagonizes UVR-induced immunosuppression through two mechanisms: reduction of UVR-induced DNA damage and inhibition of UVR-induced regulatory T cells.
J Invest Dermatol
; 130(2): 554-62, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-19727119
ABSTRACT
UVR-induced DNA damage is the major molecular trigger for photoimmunosuppression. The cytokines IL-12 and IL-18, which reduce DNA damage through induction of DNA repair, prevent UVR-induced immunosuppression. IL-12 but not IL-18 can break established UVR-induced immunotolerance through modulation of regulatory T cells (Treg). IL-23 is related to IL-12 by sharing the p40 subunit. Hence, we studied whether (i) IL-23 can reduce UVR-induced DNA damage and thereby prevent UVR-induced immunosuppression and (ii) can suppress the activity of Treg. IL-23 reduced UVR-induced apoptosis of keratinocytes. Injection of IL-23 into UVR-exposed mice diminished the number of apoptotic keratinocytes and the amounts of DNA damage. This was not observed in DNA repair-deficient xeroderma pigmentosum A knock-out mice (Xpa-KO mice), implying that IL-23 reduces DNA damage through induction of DNA repair. Similarly, UVR-mediated suppression of the induction of contact hypersensitivity was prevented on injection of IL-23 in wild-type but not in Xpa-KO mice. However, in contrast to IL-18, IL-23 inhibited the activity of UVR-induced Treg as demonstrated by adoptive transfer experiments. Our data indicate that IL-23, similar to IL-12 and IL-18, can reduce UVR-induced DNA damage and thereby prevent immunosuppression. IL-23 shares with IL-12 the still unique capacity to restore suppressed immune responses because of its effect on Treg.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Interleucina-12
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Interleucina-18
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Interleucina-23
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Imunossupressores
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article