P2X7 receptor in skin biology and diseases

Abstract

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.

The P2X7 receptor is not essential for development of imiquimod-induced psoriasis-like inflammation in mice

“…Therefore, P2X7 may be up-regulated on keratinocytes due to IFN-γ present in IMQ-treated skin. Alternatively, since P2X7 is also found on various skin immune cells [8], increased P2X7 expression in IMQtreated ears may simply reflect increased numbers of infiltrating leukocytes in IMQ-induced skin as observed in the current study.…”

“…However, given the potential roles of P2X7 in human psoriasis [13,14] and other skin diseases [8], a role for this receptor in human psoriasis or other mouse models of this disease cannot be excluded. …”

“…P2X7 is present on keratinocytes [9] and immune cells important in psoriasis including neutrophils [10], macrophages [11] and T cells [12], where its activation can drive cytokine release and potentially promote inflammation [8]. Notably, IFN-γ can upregulate the expression of P2X7 in primary keratinocytes [13] and P2X7 expression is increased in human psoriatic lesions [13,14].…”

“…The ATP-gated P2X7 receptor channel has been implicated in a number of skin diseases including psoriasis [8]. P2X7 is present on keratinocytes [9] and immune cells important in psoriasis including neutrophils [10], macrophages [11] and T cells [12], where its activation can drive cytokine release and potentially promote inflammation [8].…”

The P2X7 receptor antagonist Brilliant Blue G reduces serum human interferon-γ in a humanized mouse model of graft-versus-host disease

“…P2X7 is an ATP-gated cation channel, whereby activation by ATP allows the flux of Ca 21 , K 1 and other cations, including fluorescent dyes [9]. P2X7 is present on numerous immune cell types, including antigen-presenting cells and T cells [10]. Activation of the P2X7 receptor can result in a variety of downstream signalling events, including cytokine release, reactive oxygen species formation and cell proliferation [11].…”