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  • Adenosine and cAMP signaling skew human dendritic ...

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

Read time: 1 mins
Published:25th Mar 2020
Source: Immunology
Multiple endogenous mechanisms that regulate immune and inflammatory processes contribute to the maintenance of peripheral tolerance and prevent chronic inflammation in mammals. Yet pathogens and tumors are able to exploit these homeostatic pathways to foster immunosuppressive microenvironments and evade immune surveillance. The release of adenosine in the extra-cellular 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 tumor 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.

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