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-beta. 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

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

RONCHETTI, Simona;NOCENTINI, Giuseppe;PETRILLO, MARIA GRAZIA;BIANCHINI, RODOLFO;SPORTOLETTI, PAOLO;BASTIANELLI, ALESSANDRA;AYROLDI, Emira Maria;RICCARDI, Carlo
2011

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-beta. 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
2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/457495
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