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.
Ronchetti
Simona
S
Pharmacology, Toxicology and Chemotherapy Section, Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, 06122, Italy. simoronc@unipg.it
Nocentini
Giuseppe
G
Petrillo
Maria Grazia
MG
Bianchini
Rodolfo
R
Sportoletti
Paolo
P
Bastianelli
Alessandra
A
Ayroldi
Emira M
EM
Riccardi
Carlo
C
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse