Dataset Information

Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance.

ABSTRACT: The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8?+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8?+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens. The absence of CD8?+ DCs or CD36 altered thymic T cell selection, as evidenced by TCR repertoire analysis and the loss of allo-tolerance in murine allogeneic BM transplantation (allo-BMT) studies. Decreases in these DCs and CD36 expression in peripheral blood of human allo-BMT patients correlated with graft-versus-host disease. Our findings suggest that CD36 facilitates transfer of mTEC-derived cell-surface antigen on CD8?+ DCs to promote tolerance to host antigens during homeostasis and allo-BMT.

SUBMITTER: Perry JSA

PROVIDER: S-EPMC5986080 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance.

Perry Justin S A JSA Russler-Germain Emilie V EV Zhou You W YW Purtha Whitney W Cooper Matthew L ML Choi Jaebok J Schroeder Mark A MA Salazar Vanessa V Egawa Takeshi T Lee Byeong-Chel BC Abumrad Nada A NA Kim Brian S BS Anderson Mark S MS DiPersio John F JF Hsieh Chyi-Song CS

Immunity 20180508 5

The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α<sup>+</sup> dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α<sup>+</su ...[more]

PMID: 29752065

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Project description:Graphene nanoplatelets (GNPs) are novel two-dimensional engineered nanomaterials consisting of planar stacks of graphene. Although human exposures are increasing, our knowledge is lacking regarding immune-specific responses to GNPs and mechanisms of interactions. Our current study utilizes a metabolite profiling approach to evaluate macrophage responses to GNPs. Furthermore, we assessed the role of the scavenger receptor CD36 in mediating these GNP-induced responses. GNPs were purchased with dimensions of 2 ?m × 2 ?m × 12 nm. Macrophages were exposed to GNPs at different concentrations of 0, 25, 50, or 100 ?g/ml for 1, 3, or 6 h. Following exposure, no cytotoxicity was observed, while GNPs readily associated with macrophages in a concentration-dependent manner. After the 1h-pretreatment of either a CD36 competitive ligand sulfo-N-succinimidyl oleate (SSO) or a CD36 specific antibody, the cellular association of GNPs by macrophages was significantly reduced. GNP exposure was determined to alter mitochondrial membrane potential while the pretreatment with a CD36 antibody inhibited these changes. In a separate exposure, macrophages were exposed to GNPs at concentrations of 0, 50, or 100 ?g/mL for 1 or 3h or 100 ?M SSO (a CD36 specific ligand) for 1h and collected for metabolite profiling. Principal component analysis of identified compounds determined differential grouping based on exposure conditions. The number of compounds changed following exposure was determined to be both concentration- and time-dependent. Identified metabolites were determined to relate to several metabolism pathways such as glutathione metabolism, Pantothenate and CoA biosynthesis, Sphingolipid metabolism, Purine metabolism, arachidonic acid metabolism and others. Lastly, a number of metabolites were found in common between cells exposed to the CD36 receptor ligand, SSO, and GNPs suggesting both CD36-dependent and independent responses to GNP exposure. Together our data demonstrates GNP-macrophage interactions, the role of CD36 in the cellular response, and metabolic pathways disrupted due to exposure.

Dataset Information

Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance.

Publications

Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance.

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