IL-21 May Promote Granzyme B-Dependent NK/Plasmacytoid Dendritic Cell Functional Interaction in Cutaneous Lupus Erythematosus.
J Invest Dermatol
; 137(7): 1493-1500, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28344062
ABSTRACT
Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only T helper 1/T helper 17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I IFNs. In lupus erythematosus skin lesions, the percentage of GrB+ pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tunes the levels of pDC-dependent GrB also in vivo. In lupus erythematosus, pDCs colocalized with professional cytotoxic cells at sites of epithelial damage, suggesting a role in keratinocyte killing. Accordingly, we demonstrate that supernatants of IL-21-activated pDCs promoted autologous keratinocyte killing by natural killer cells and this action was dependent on GrB. These results propose a GrB-dependent functional interaction between pDCs and natural killer cells and highlight a negative feedback regulation by type I IFNs in vitro and in vivo that may function to limit excessive tissue damage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Lúpus Eritematoso Cutâneo
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Células Matadoras Naturais
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Citocinas
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Interleucinas
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Granzimas
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article