Publication Date:
2014-07-22
Description:
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- 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.
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Permalink
