CD25 as an immune regulatory molecule expressed on myeloid dendritic cells

Driesen, Julia; Попов, А. В.; Schultze, Joachim L.

doi:10.1016/j.imbio.2008.07.026

Cited by 62 publications

(59 citation statements)

References 79 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR agonists or pro-inflammatory cytokines. 36 Our results show that CD25 expression can also be induced in iDCs by an adenosine analogue and, more broadly, by signals that trigger intra-cellular cAMP up-regulation. In addition, the inhibitory receptors ILT-3 and ILT-4, known to exert immunoregulatory functions on T-cell stimulation by DCs, 37 were also expressed on the cell surface as a consequence of AR ligation by NECA or in the presence of FSK/IBMX (Fig.…”

Section: Discussionmentioning

confidence: 58%

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity

et al. 2013

View full text Add to dashboard Cite

SummaryMultiple endogenous mechanisms that regulate immune and inflammatory processes contribute to the maintenance of peripheral tolerance and prevent chronic inflammation in mammals. Yet pathogens and tumours are able to exploit these homeostatic pathways to foster immunosuppressive microenvironments and evade immune surveillance. The release of adenosine in the extracellular space contributes to these phenomena by exerting a broad range of immunomodulatory effects. Here we document the influence of adenosine receptor triggering on human dendritic cell differentiation and functions. We show that the expression of several immunomodulatory proteins and myeloid/monocytic lineage markers was affected by adenosine receptors and the cAMP pathway. These changes were reminiscent of the phenotype associated with tolerogenic dendritic cells and, functionally, translated into a defective capacity to prime CD8 + T-cells with a common tumour antigen in vitro. These results establish a novel mechanism by which adenosine hampers CD8 + T-cell immunity via dendritic cells that may contribute to peripheral tolerance as well as to the establishment of immunosuppressive microenvironments relevant to tumour biology.

show abstract

Section: Discussionmentioning

confidence: 58%

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity

et al. 2013

View full text Add to dashboard Cite

show abstract

“…These markers are mainly expressed by activated and regulatory T cells and represent cell surface proteins involved in signal transduction (29Y33). CD25 is the >-subunit of the interleukin (IL)-2 receptor, which is important in the regulation of the survival and proliferation of T cells (30,31). LAG-3 or CD223 is an activation-induced marker involved in the negative regulation of homeostasis and T-cell function (29,33).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Polymerase Chain Reaction Profiling of Immunomarkers in Rejecting Kidney Allografts for Predicting Response to Steroid Treatment

Rekers

Bajema²,

Mallat³

et al. 2012

Transplantation

View full text Add to dashboard Cite

show abstract

“…We then hypothesized that mDCs are activated by the IL-2 signal and that this activation is necessary for effective priming of antigen-specific T cells. However, this hypothesis turned out to be incorrect, because myeloid DCs, whether in the resting or activated state, do not express CD122, and therefore cannot receive an IL-2 (or IL-15) signal [45,73].…”

Section: Moa Of Daclizumab On the Human Immune Systemmentioning

confidence: 99%

Daclizumab Therapy for Multiple Sclerosis

Bielekova

2013

Neurotherapeutics

View full text Add to dashboard Cite

Daclizumab is a humanized monoclonal antibody of IgG1 subtype that binds to the Tac epitope on the interleukin-2 (IL-2) receptor α-chain (CD25), thus, effectively blocking the formation of the high-affinity IL-2 receptor. Because the high-affinity IL-2 receptor signaling promotes expansion of activated T cells in vitro, daclizumab was designed as a therapy that selectively inhibits T-cell activation. Assuming the previous statement, daclizumab received regulatory approval as add-on therapy to standard immunosuppressive regimen for the prevention of acute allograft rejection in renal transplantation. Based on its putative mechanism of action (MOA), daclizumab represented an ideal therapy for T-cell-mediated autoimmune diseases and was subsequently tested in inflammatory uveitis and multiple sclerosis (MS). In both of these diseases, daclizumab therapy significantly inhibited target organ inflammation. Mechanistic studies in MS demonstrated that the MOA of daclizumab is surprisingly broad and that the drug exerts unexpected effects on multiple components of the innate immune system. Specifically, daclizumab dramatically expands and activates immunoregulatory CD56 bright NK cells, which gain access to the intrathecal compartment in MS and can kill autologous activated T cells. Daclizumab also blocks trans-presentation of IL-2 by mature dendritic cells to primed T cells, resulting in profound inhibition of antigen-specific T cells. Finally, daclizumab modulates the development of innate lymphoid cells. In conclusion, daclizumab therapy, which is currently in phase III testing for inflammatory MS, has a unique MOA that does not limit migration of immune cells into the intrathecal compartment, but rather provides multifactorial immunomodulatory effects with resultant inhibition of MS-related inflammation.

show abstract

CD25 as an immune regulatory molecule expressed on myeloid dendritic cells

Cited by 62 publications

References 79 publications

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity

Quantitative Polymerase Chain Reaction Profiling of Immunomarkers in Rejecting Kidney Allografts for Predicting Response to Steroid Treatment

Daclizumab Therapy for Multiple Sclerosis

Contact Info

Product

Resources

About

CD25 as an immune regulatory molecule expressed on myeloid dendritic cells

Cited by 62 publications

References 79 publications

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8+ T‐cell priming capacity

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8+ T‐cell priming capacity

Quantitative Polymerase Chain Reaction Profiling of Immunomarkers in Rejecting Kidney Allografts for Predicting Response to Steroid Treatment

Daclizumab Therapy for Multiple Sclerosis

Contact Info

Product

Resources

About

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8⁺ T‐cell priming capacity