scholarly journals Erratum: Interleukin-10 receptor-1 expression in monocyte-derived antigen-presenting cell populations: dendritic cells partially escape from IL-10's inhibitory mechanisms

2015 ◽  
Vol 16 (5) ◽  
pp. 366-366 ◽  
Author(s):  
S von Haehling ◽  
K Wolk ◽  
C Höflich ◽  
S Kunz ◽  
B H Grünberg ◽  
...  
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4897-4897 ◽  
Author(s):  
Phillip Fromm ◽  
Michael Papadimitrious ◽  
Jennifer Hsu ◽  
Stephen Robert Larsen ◽  
John Gibson ◽  
...  

Abstract Dendritic cells (DC) are phenotypically identified in human blood as HLA-DR+ cells, which lack major cell surface lineage markers. We demonstrated that myeloid antigen presenting cells, including monocytes and DC display a continuum of CD14 and CD16 expression (10th Human Leucocyte Differentiation Antigen Workshop). The robustness of DC and monocyte identification, particularly when identifying cell subsets with little or no surface CD14 is limited by subjective gating strategies for determining rare cell populations. Application of Poisson counting statistics established that rare cell types such as "CD14- CD16+ DC" are often overlooked in analyses powered to detect the much larger populations of "classical" and "non-classical" monocytes. We used fluorescent and mass cytometry, in conjunction with unsupervised high dimensional clustering, to show that the continuum of CD14 expression separates CD14lo CD16+ non-classical monocytes and CD14- CD16+ DC. We have defined the CD14-CD16+ DC using a broad panel of cell surface markers and established a CD14-CD16+ DC phenotypic signature that is distinct from both classical and non-classical monocytes in healthy donor blood. The CD14-CD16+ DC differ in both size to CD14lo CD16+ monocytes and functional antigen uptake, with slower kinetics of soluble antigen uptake into lysozymes. Their proteasome processing and presentation of influenza matrix protein by MHC I was comparable to other primary blood monocytes and DC antigen presenting cell populations. The CD14-CD16+ DC had limited capacity for further in vitro differentiation. The recovery of CD14-CD16+ DC after autologous and allogeneic myeloablative hematopoietic cell transplants (HCT) followed similar kinetics to other monocytic and DC populations. CD14lo CD16+ monocytes expressed CCR5 as did other myeloid DC but CD14-CD16+ DC lacked CCR5, although interferon induced CCR5. The early differentiation and induction of CCR5 on circulating CD16+ DC after allogeneic HCT predicted for the onset of acute graft versus host disease. These data demonstrate that "CD14- CD16+ DC" represents a distinct clinically relevant human white blood cell population, whose ontogeny and function are under further investigation. Disclosures Fromm: DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Papadimitrious:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Hsu:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Larsen:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Gibson:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Bradstock:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Kupresanin:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Clark:DendroCyte BioTech Ltd: Equity Ownership, Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Hart:DendroCyte BioTech Ltd: Equity Ownership, Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd.


2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Cleo Goyvaerts ◽  
Karine Breckpot

In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypesin situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.


Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3376-3382 ◽  
Author(s):  
Li Wu ◽  
Angela D'Amico ◽  
Hubertus Hochrein ◽  
Meredith O'Keeffe ◽  
Ken Shortman ◽  
...  

Abstract The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8α, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin−c-kit+Thy-1lowCD4low) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4−CD8α+ DCs, whereas CMPs produced similar numbers of CD4−CD8α+ and CD4+CD8α− DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8α does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.


2006 ◽  
Vol 74 (12) ◽  
pp. 6700-6706 ◽  
Author(s):  
Britta C. Urban ◽  
Damien Cordery ◽  
Mohammed J. Shafi ◽  
Peter C. Bull ◽  
Christopher I. Newbold ◽  
...  

ABSTRACT The ability of Plasmodium falciparum-infected erythrocytes to adhere to host endothelial cells via receptor molecules such as ICAM-1 and CD36 is considered a hallmark for the development of severe malaria syndromes. These molecules are also expressed on leukocytes such as dendritic cells. Dendritic cells are antigen-presenting cells that are crucial for the initiation of adaptive immune responses. In many human diseases, their frequency and function is perturbed. We analyzed the frequency of peripheral blood dendritic cell subsets and the plasma concentrations of interleukin-10 (IL-10) and IL-12 in Kenyan children with severe malaria and during convalescence and related these parameters to the adhesion phenotype of the acute parasite isolates. The frequency of CD1c+ dendritic cells in children with acute malaria was comparable to that in healthy controls, but the frequency of BDCA3+ dendritic cells was significantly increased. Analysis of the adhesion phenotypes of parasite isolates revealed that adhesion to ICAM-1 was associated with the frequency of peripheral blood CD1c+ dendritic cells, whereas the adhesion of infected erythrocytes to CD36 correlated with high concentrations of IL-10 and low concentrations of IL-12 in plasma.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenyan Fu ◽  
Renfei Cai ◽  
Zetong Ma ◽  
Tian Li ◽  
Changhai Lei ◽  
...  

The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual antigen presenting cells (APCs), the decidual dendritic cells (dDCs), and decidual macrophages (dMϕs) increased the production of interleukin 10 and induced the decidua APCs to powerfully polarize the decidual CD4+ T cells toward a classic TH2 phenotype. We further proposed that Notch signaling shows a pivotal effect on the transcriptional regulation in decidual immune cell subsets. Moreover, the administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in an abortion-prone animal model stress. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.


2021 ◽  
Vol 22 (15) ◽  
pp. 7970
Author(s):  
Maaike Suuring ◽  
Aurélie Moreau

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn’s disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.


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