Dataset Information

NKG2D receptor regulates human effector T-cell cytokine production.

ABSTRACT: Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8(+) T cells. Stimulation of CD8(+) T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3?, activated ?-catenin and increased expression of ?-catenin-induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-? in a ?-catenin- and PPAR?- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8(+) T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex.

SUBMITTER: Barber A

PROVIDER: S-EPMC3123023 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NKG2D receptor regulates human effector T-cell cytokine production.

Barber Amorette A Sentman Charles L CL

Blood 20110425 24

Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8(+) T cells. Stimulation of CD8(+) T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin-i ...[more]

PMID: 21518928

Similar Datasets

Project description:UNLABELLED:Previous studies demonstrated that targeted deletion of the Ron receptor tyrosine kinase (TK) domain in mice leads to marked hepatocyte protection in a well-characterized model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (GalN)-sensitized mice. Hepatocyte protection in TK-/- mice was observed despite paradoxically elevated serum levels of tumor necrosis factor alpha (TNF-?). To understand the role of Ron in the liver, purified populations of Kupffer cells and hepatocytes from wildtype (TK+/+) and TK-/- mice were studied. Utilizing quantitative reverse-transcription polymerase chain reaction (RT-PCR), we demonstrated that Ron is expressed in these cell types. Moreover, we also recapitulated the protected hepatocyte phenotype and exaggerated cytokine production observed in the TK-/- mice in vivo through the use of purified cultured cells ex vivo. We show that isolated TK-/- Kupffer cells produce increased levels of TNF-? and select cytokines compared to TK+/+ cells following LPS stimulation. We also show that conditioned media from LPS-treated TK-/- Kupffer cells was more toxic to hepatocytes than control media, suggesting the exaggerated levels of cytokines produced from the TK-/- Kupffer cells are detrimental to wildtype hepatocytes. In addition, we observed that TK-/- hepatocytes were more resistant to cell death compared to TK+/+ hepatocytes, suggesting that Ron functions in both the epithelial and inflammatory cell compartments to regulate acute liver injury. These findings were confirmed in vivo in mice with hepatocyte and macrophage cell-type-specific conditional Ron deletions. Mice with Ron loss selectively in hepatocytes exhibited less liver damage and increased survival compared to mice with Ron loss in macrophages. CONCLUSION:We dissected cell-type-specific roles for Ron such that this receptor modulates cytokine production from Kupffer cells and inhibits hepatocyte survival in response to injury.

Dataset Information

NKG2D receptor regulates human effector T-cell cytokine production.

Publications

NKG2D receptor regulates human effector T-cell cytokine production.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets