Dual requirement for STAT signaling in dendritic cell immunobiology

Gloria Donninelli, Isabella Sanseverino, Cristina Purificato, Sandra Gessani, Maria Cristina Gauzzi

Research output: Contribution to journalArticle

Abstract

Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature that is currently being exploited in DC-based therapies. We previously reported that the small-molecule Stattic, originally developed as a STAT3-specific inhibitor, also inhibits STAT1 and STAT2 phosphorylation in DC exposed to cytokines or LPS. Aim of this study was to investigate the functional consequences of in vitro treatment with Stattic on DC immunobiology. Interestingly, we observed an opposite effect of Stattic on DC immunophenotype depending on the activation state. While the expression of costimulatory, coinhibitory, MHC class II and CD83 molecules was enhanced in immature DC exposed to Stattic, the LPS induced up-modulation of these molecules was strongly repressed. An effective blockade of LPS-induced secretion of proinflammatory cytokines and capacity to stimulate a Th1 polarization was also observed in the presence of Stattic. Our results indicate that the immunological consequences of STAT inhibition in DC vary depending on the cell activation state. This knowledge is of relevance for anticipating potential effects of STAT-targeted therapeutics, and pursuing selective DC manipulation in clinical applications.

Original languageEnglish
JournalImmunobiology
DOIs
Publication statusAccepted/In press - Jan 1 2017

Keywords

  • Cytokine
  • Dendritic cell
  • Small molecule inhibitor
  • STAT

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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