Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Peptide Super-Agonist Enhances T-Cell Responses to Melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

The activation of dendritic cells (DCs) has profound implications and governs the control of adaptive immunity. However, long-term activation might drive exhaustion of immune cells and negatively affect functionality. Here, long-term vs. short-term exposure to bacterial lipopolysaccharide and interferon (IFN)γ was evaluated on human monocyte-derived DCs. Long-term activated DC1s began to undergo apoptosis concomitant with a profound TAM-receptor and efferocytosis-dependent induction of interleukin (IL)-10. Whereas, levels of IL-12p70 and IL-10 were positively correlated upon short-term activation, an inverse association occured upon long-term activation and, while short-term activated CD1a+ DCs were main producers of IL-12p70, CD1a- DCs were the main fraction that underwent apoptosis and released IL-10 upon long-term activation. Moreover, pre-apoptotic long-term activated DCs were no longer able to activate alloreactive IFNγ-responsive T cells present in peripheral blood mononuclear cells from healthy volunteers. The IFNγ response was mediated by IL-12p70, as a strong reduction in IFNγ was observed following blockade with an IL-12p70 neutralizing antibody. Finally, multiplex analysis of DC supernatants revealed a particular pattern of proteins associated with apoptosis, cancer and chronic inflammation partly overlapping with gold standard DCs well-known for their inability to secrete IL-12p70. In conclusion, long-term activated DC1s significantly changed their profile toward a non-functional, tumor-promoting and anti-inflammatory phenotype.

Original languageEnglish
JournalFrontiers in Immunology
Volume10
Pages (from-to)2702
ISSN1664-3224
DOIs
Publication statusPublished - 21 Nov 2019

ID: 59226797