Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis

Mark H. Wenink, Kim C. M. Santegoets, John Butcher, Lenny van Bon, Femke G. M. Lamers-Karnebeek, Wim B. van den Berg, Piet L. C. M. van Riel, Iain B. McInnes, Timothy R. D. J. Radstake

Research output: Contribution to journalArticle

Abstract

Objective
The pathogenesis of psoriatic arthritis (PsA) remains poorly understood. The underlying chronic inflammatory immune response is thought to be triggered by unknown environmental factors potentially arising from a defective immune function. We undertook this study to determine whether an impaired acute inflammatory response by dendritic cells (DCs) might compromise the clearance of bacteria and predispose to chronic inflammation.
Methods
We determined cytokine production by DCs from healthy controls and from patients with rheumatoid arthritis, PsA, and psoriasis in response to Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, and a range of other bacteria and Toll-like receptor (TLR) ligands. Phenotypic differences involved in cellular responses against (myco) bacteria were determined by quantitative polymerase chain reaction and flow cytometry.
Results
The secretion of proinflammatory cytokines by PsA DCs was impaired upon in vitro challenge with mycobacteria and TLR-2 ligands. This impairment was associated with elevated serum levels of C-reactive protein. The expression of TLR-2 and other receptors known to mediate mycobacterial recognition was unaltered. In contrast, the intracellular TLR inhibitors suppressor of cytokine signaling 3 and A20 were more highly expressed in DCs from PsA patients. PsA DCs further demonstrated up-regulated levels of ATG16L1, NADPH oxidase 2, and LL37, which are molecules implicated in the immune response against intracellular bacteria.
Conclusion
Our findings indicate that DCs from PsA patients have a disordered immune response toward some species of (myco) bacteria. This might predispose to impaired immune responses to, and in turn impaired clearance of, these bacteria, setting the stage for the chronic inflammation of joints, entheses, skin, and the gut.
Original languageEnglish
Pages (from-to)3313-3322
Number of pages10
JournalArthritis and Rheumatism
Volume63
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Psoriatic arthritis, dendritic cell, cytokine

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