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

Abstract 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.