Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

Granstein, Richard D.; Ding, Wanhong; Huang, Jing; Holzer, Aton M.; Gallo, Richard L.; Nardo, Anna Di; Wagner, John A.

doi:10.4049/jimmunol.174.12.7725

Cited by 52 publications

(32 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Adenosine is recognized by the A2A GPCR on DCs and it conditions the cells to become anti-inflammatory, limiting DC activation 89,90 . ATP can also be sensed by P2YRs, which are GPCRs that promote DC migration 91 , or through ligand-gated ion channels (P2XRs) that provide an activating signal 92 and stimulate the caspase 1-dependent cleavage and secretion of IL-1β 93 (FIG. 3).…”

Section: Signalling By Exogenous Metabolites In Dcsmentioning

confidence: 99%

Dendritic cell metabolism

2014

View full text Add to dashboard Cite

The past 15 years have seen enormous advances in our understanding of the receptor and signalling systems that allow dendritic cells (DCs) to respond to pathogens or other danger signals and initiate innate and adaptive immune responses. We are now beginning to appreciate that many of these pathways not only stimulate changes in the expression of genes that control DC immune functions, but also affect metabolic pathways, thereby integrating the cellular requirements of the activation process. In this Review, we focus on this relatively new area of research and attempt to describe an integrated view of DC immunometabolism.

show abstract

Section: Signalling By Exogenous Metabolites In Dcsmentioning

confidence: 99%

Dendritic cell metabolism

2014

View full text Add to dashboard Cite

show abstract

“…Strategies to enhance IL-1-mediated responses might include: activating TLRs using TLR agonists 99 ; enhancing inflammasome activation (for example, through the administration of alum 100 , nanoparticles 101 or ATPγS 102 (a form of ATP that is stable in vivo and activates P2X7)); administering recombinant IL-1α or IL-1β to infected skin 26 ; and enhancing IL-1R signalling by administering neutralizing antibodies specific for IL-1RA or the decoy receptor IL-1R2 (REF. 15).…”

Section: Potential Immunotherapy Against S Aureusmentioning

confidence: 99%

Immunity against Staphylococcus aureus cutaneous infections

2011

View full text Add to dashboard Cite

Complications arising from cutaneous and soft tissue infections with Staphylococcus aureus are a major clinical problem owing to the high incidence of these infections and the widespread emergence of antibiotic-resistant bacterial strains. If prophylactic vaccines or immunotherapy for certain patient populations are to be developed as an alternative to antibiotics, it will be essential to better understand the immune mechanisms that provide protection against S. aureus skin infections. Recent discoveries have identified a key role for interleukin-1 (IL-1)- and IL-17-mediated immune responses in promoting neutrophil recruitment to the site of infection in the skin, a process that is required for host defence and bacterial clearance. This Review describes these new insights and discusses their potential impact on immune-based therapies and vaccination strategies.

show abstract

“…However, ATPgS cannot activate murine P2X7 in vitro [90] despite activating other mammalian P2X7 [90,91] . This raises the possibility that ATPgS acts on other P2 receptors in this model of murine CHS [31] . Notably, nonmetal haptens can induce ATP release from primary human and HaCaT keratinocytes [92] providing a possible source for extracellular ATP in ACD.…”

Section: Allergic Contact Dermatitismentioning

confidence: 99%

“…This impaired CHS response is due to the absence of P2X7-mediated IL-1b release from DCs abrogating the sensitising capacity of these cells [89] . Intradermal injection of the hydrolysis-resistant nucleotide, adenosine gammathiotriphosphate (ATPgS), can also enhance the CHS response in mice [31] indirectly supporting a role for P2X7…”

Section: Allergic Contact Dermatitismentioning

confidence: 99%

“…Further, P2X7 is present on human LCs derived from monocytes in vitro and activation of this receptor results in the rapid shedding of CD23 (the low affinity IgE receptor) from these cells [22] . Finally, P2X7 is present on the murine LC-like line, XS106, and activation of this receptor results in the release of IL-1b from these cells [31] . Collectively, these studies support a role for P2X7 activation on LCs in promoting inflammation and immunity.…”

Section: Langerhans Cellsmentioning

confidence: 99%

See 1 more Smart Citation

P2X7 receptor in skin biology and diseases

Geraghty¹,

Watson²,

Adhikary³

et al. 2016

WJD

View full text Add to dashboard Cite

The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. AbstractThe P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. Core tip: The P2X7 receptor is present on immune, stromal and epithelial cells. Activation of this receptor by its natural ligand, extracellular adenosine triphosphate, causes a variety of downstream effects including release of inflammatory mediators and growth factors, as well as cell death. P2X7 has various functions on skin cells, and studies of mouse models of disease and of human cells and tissues highlight emerging roles for this receptor in common skin disorders.

show abstract

Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

Cited by 52 publications

References 22 publications

Dendritic cell metabolism

Dendritic cell metabolism

Immunity against Staphylococcus aureus cutaneous infections

P2X7 receptor in skin biology and diseases

Contact Info

Product

Resources

About