Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation

G Varga, J Ehrchen, A Brockhausen, T Weinhage, N Nippe, M Belz, A Tsianakas, M Ross, D Bettenworth, T Spieker, M Wolf, R Lippe, K Tenbrock, Pieter Leenen, J Roth, C Sunderkotter

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24 Citations (Scopus)

Abstract

Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work revealed that GCs induced a stable anti-inflammatory phenotype in monocytes, the GC-stimulated monocytes (GCsMs) that we exploited for targeted GC-mediated therapeutic effects. We demonstrate that GCsMs interact with T cells in suppressing proliferation, as well as cytokine release of CD8(+) and, especially, CD4(+) T cells in vitro, and that they support generation of Foxp3(+) cells. Therefore, we tested their immunosuppressive potential in CD4(+) T cell-induced colitis in vivo. We found that injection of GCsMs into mice with severe colitis abolished the inflammation and resulted in significant clinical improvement within a few days. T cells recovered from GCsM-treated mice exhibited reduced secretion of proinflammatory cytokines IFN-gamma and IL-17. Furthermore, clusters of Foxp3(+) CD4(+) T cells were detectable at local sites of inflammation in the colon. Thus, GCsMs are able to modify T cell responses in vitro and in vivo, as well as to downregulate and clinically cure severe T cell-mediated colitis.
Original languageUndefined/Unknown
Pages (from-to)1090-1099
Number of pages10
JournalJournal of Immunology
Volume193
Issue number4
DOIs
Publication statusPublished - 2014

Research programs

  • EMC MM-02-72-02

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