ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2013
Rapamycin augments human DC IL-12p70 and IL-27 secretion to promote allogeneic Type 1 polarization modulated by NK cells.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- RAD001-mediated mTOR targeting in human monocyte-derived dendritic cells shifts them toward an immunogenic phenotype.Immunologic research · 2024Article
- Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses.Biomedicines · 2024Article
- Human Regulatory Macrophages Derived from THP-1 Cells Using Arginylglycylaspartic Acid and Vitamin D3.Biomedicines · 2023Article
- Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12 Prevents Gut Dysbiosis and Inflammation.Journal of Crohn's & colitis · 2022Article
- Cyclosporine A, in Contrast to Rapamycin, Affects the Ability of Dendritic Cells to Induce Immune Tolerance Mechanisms.Archivum immunologiae et therapiae experimentalis · 2021Article
- Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition.Scientific reports · 2021Article
- Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury.International journal of molecular sciences · 2021Article
- Mesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis.Theranostics · 2019Article
- Effects of Antirejection Drugs on Innate Immune Cells After Kidney Transplantation.Frontiers in immunology · 2019Review
- High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.Cellular immunology · 2018Article
- Rapamycin Synergizes with Cisplatin in Antiendometrial Cancer Activation by Improving IL-27-Stimulated Cytotoxicity of NK Cells.Neoplasia (New York, N.Y.) · 2018Article
- DHRS9 Is a Stable Marker of Human Regulatory Macrophages.Transplantation · 2017Article
- Glucose represses dendritic cell-induced T cell responses.Nature communications · 2017Article
- mTOR-Mediated Regulation of Dendritic Cell Differentiation and Function.Trends in immunology · 2016Review
- Article
- Regulation of innate immune cell function by mTOR.Nature reviews. Immunology · 2015Review
- Tempering allorecognition to induce transplant tolerance with chemically modified apoptotic donor cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2015Review
- mTORC2 Deficiency in Myeloid Dendritic Cells Enhances Their Allogeneic Th1 and Th17 Stimulatory Ability after TLR4 Ligation In Vitro and In Vivo.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Regulatory myeloid cells in transplantation.Transplantation · 2014Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mammalian target of rapamycin kinase inhibitor (mTORi) rapamycin (RAPA) use in transplantation can lead to inflammatory complications in some patients. Our goal was to better understand how mTORi-exposed human monocyte-derived dendritic cells (DC) stimulated with pro-inflammatory cytokines shape T cell allo-immunity. RAPA-conditioned-DC (RAPA-DC) displayed a more immature phenotype than untreated, control (CTRL)-DC. However, subsequent exposure of RAPA-DC to an inflammatory cytokine cocktail (ICC) plus IFN-γ induced a mature Type-1 promoting phenotype, consisting of elevated HLA-DR and co-stimulatory molecules, augmented IL-12p70 and IL-27 production, but decreased IL-10 secretion compared to CTRL-DC. Co-culture of mature (m)RAPA-DC with allogeneic peripheral blood mononuclear cells resulted in significantly increased Type-1 (IFN-γ) responses by T cells. Moreover, NK cells acted as innate modulators that conveyed activating cell-to-cell contact signals in addition to helper (IFN-γ) and/or regulatory (IL-10) soluble cytokines. We conclude that production of IL12-p70, IL-27 and low IL-10 by RAPA-DC allowed us to elucidate how these cytokines as well as NK-DC interaction shapes T cell allo-immunity. Thus, lack of inhibitory NK cell function during allo-specific T cell activation by human ICC + IFN-γ-stimulated RAPA-DC may represent an unwanted effector mechanism that may underlie RAPA-induced inflammatory events in transplant patients undergoing microbial infection or allograft rejection.
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