Glucocorticoid-Induced TNFR family Related gene (GITR) enhances dendritic cell activity

Glucocorticoid-Induced TNFR family Related gene (GITR), a Tumor Necrosis Factor Receptor Superfamily (TNFRSF) member involved in immune/inflammatory processes, has been previously shown to regulate T cell activation. To study GITR role in antigen presenting cells, we evaluated the capability of bone marrow derived dendritic cells (BMDC) from GITR−/− mice to stimulate the activation of CD4+CD25− T lymphocytes. We found that GITR−/− BMDC are weaker stimulators of T cell proliferation than GITR+/+ BMDC, either in syngenic or allogenic BMDC/T cell co-cultures. Expression of GITR in GITR−/− BMDC restored their ability to activate T cells while GITR silencing in GITR+/+ BMDC inhibited the capability to stimulate T cells. GITR−/− BMDC showed a reduced production of the pro-inflammatory cytokine IL-6 and an increased production of the anti-inflammatory cytokine IL-10. Notably, co-culture of CD4+CD25− cells with GITR−/− BMDC originated FoxP3+ cells, secreting IL-10 and TGF-β. Finally, in vivo injection of GITR−/− OVA-loaded BMDC led to a lower cell number and a lower activated cell number in draining lymph nodes than in GITR+/+ OVA-loaded BMDC injected mice. Together, these results indicate that GITR plays a role in regulating BMDC activity.