IL-21 May Promote Granzyme B-Dependent NK/Plasmacytoid Dendritic Cell Functional Interaction in Cutaneous Lupus Erythematosus

Valentina Salvi, William Vermi, Andrea Cavani, Silvia Lonardi, Teresa Carbone, Fabio Facchetti, Daniela Bosisio, Silvano Sozzani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalJournal of Investigative Dermatology
Volume137
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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