1. Glucocorticoid-Induced TNFR family Related gene (GITR) enhances dendritic cell activity.
- Author
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Ronchetti S, Nocentini G, Petrillo MG, Bianchini R, Sportoletti P, Bastianelli A, Ayroldi EM, and Riccardi C
- Subjects
- Animals, Bone Marrow Cells cytology, Cytokines genetics, Cytokines immunology, Dendritic Cells cytology, Glucocorticoid-Induced TNFR-Related Protein, Lymphocyte Activation genetics, Mice, Mice, Inbred BALB C, Mice, Knockout, Receptors, Nerve Growth Factor genetics, Receptors, Tumor Necrosis Factor genetics, T-Lymphocytes, Regulatory cytology, Bone Marrow Cells immunology, Dendritic Cells immunology, Lymphocyte Activation immunology, Receptors, Nerve Growth Factor immunology, Receptors, Tumor Necrosis Factor immunology, T-Lymphocytes, Regulatory immunology
- 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
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