1. Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation.
- Author
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Varga, Georg, Ehrchen, Jan, Brockhausen, Anne, Weinhage, Toni, Nippe, Nadine, Beiz, Michael, Tsianakas, Athanasios, Ross, Matthias, Bettenworth, Dominik, Spieker, Tilmann, Wolf, Marc, Lippe, Ralph, Tenbrock, Klaus, Leenen, Pieter J. M., Roth, Johannes, and Sunderkötter, Cord
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MONOCYTES , *IMMUNOSUPPRESSION , *INFLAMMATION prevention , *T cells , *CELL proliferation ,THERAPEUTIC use of glucocorticoids - 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-γ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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