Disease relevance of TNFSF18

• We have measured the levels of GITR and GITRL in plasma from atopic dermatitis patients and found it not to be increased [1].
• B cells suppressed autoimmunity by maintenance of regulatory T cells via GITRL [2].

High impact information on TNFSF18

• This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells [3].
• We also demonstrated that pDCs localized in close contact to NK cells in T-cell areas of the tonsils, and a subpopulation of the pDCs expressed GITRL [3].
• By microarray gene expression analysis, we found that pDCs activated by virus or CpG-ODN preferentially express the ligand for the glucocorticoid-induced tumor necrosis factor receptor (GITRL), which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis [3].
• We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells [4].
• Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death [4].

Chemical compound and disease context of TNFSF18

• Glucocorticoid-induced Tumour Necrosis Factor Receptor (GITR) and its Ligand (GITRL) in Atopic Dermatitis [1].

Biological context of TNFSF18

• Multimeric soluble GITR ligand (GITRL) augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA vaccination [5].
• The upregulation of GITRL by proinflammatory cytokines suggests that GITRL may play an important role in ocular immunity [6].
• Binding of the GITR-ligand (GITRL) leads to downregulation of the regulatory function of Tregs [1].
• B cells induced proliferation of regulatory T cells via GITRL  [2]

Anatomical context of TNFSF18

• Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues [4].
• Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL) [3].
• Expression of the GITRL is restricted to immature and mature splenic dendritic cells [7].
• CONCLUSIONS: GITRL is expressed constitutively on RPE and in high levels on photoreceptor inner segments [6].
• The regulation of GITRL was investigated by culturing retinal pigment epithelium (RPE) with proinflammatory cytokines and performing immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR) [6].

Associations of TNFSF18 with chemical compounds

• Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation [8].

Regulatory relationships of TNFSF18

• Analysis of cytokine profiles revealed high level of TGF-beta during the immunosuppression by RPE cells while expression of GITRL abrogated the RPE cell-induced TGF-beta secretion [9].

Other interactions of TNFSF18

• RESULTS: Soluble hGITR (shGITR) stimulated FLSs to produce MMP-13, and blockade of hGITRL reduced this effect [10].

Analytical, diagnostic and therapeutic context of TNFSF18

• Expressions of hGITR ligand (hGITRL) on the surface of FLSs and hGITR on the surface of human CD4(+) T cells were analyzed by flow cytometry and RT-PCR [10].
• METHODS: Immunohistochemistry and confocal immunofluorescence microscopy were performed on human ocular tissue to examine the in vivo protein expression of GITRL [6].
• Remarkably, expression of GITRL on the RPE cells abrogated RPE-mediated immunosuppression of CD3(+) T cells, implicated as a possible mechanism for ocular immune privilege [9].
• Confocal immunofluorescence microscopy and flow cytometry confirmed the surface expression of GITRL on RPE cells [9].

References