P2X7 receptor in skin biology and diseases

Table 1 Events downstream of P2X7 receptor activation

RONS formation

Shedding of CD23, CD27, CD62L and E-cadherin

Up-regulation of CD80 and CD86 expression

PGE-2 synthesis and release

IL-1β and IL-18 maturation and release

IL-6 release

IL-2 and IL-17 synthesis and release

VEGF release

Killing of intracellular pathogens

Cell death

IL: Interleukin; PGE-2: Prostaglandin E2; RONS: Reactive oxygen and nitrogen species; VEGF: Vascular endothelial growth factor.

Table 2 Roles of the P2X7 receptor in mouse models of skin disease

Disease	Observations
Allergic contact dermatitis	P2X7 blockade or deficiency impairs CHS[89]
Irritant contact dermatitis	P2X7 blockade or deficiency impairs croton oil-induced oedema, IL-1β production and neutrophil infiltration[69]
Psoriasis	ND
Cutaneous graft-vs-host disease	P2X7 blockade or deficiency increases survival and reduces disease severity, serum concentrations of IFN-γ, TNF-α and IL-6 in allogeneic mouse models[98,99]
Wound healing	P2X7 deficient macrophages display reduced migration in an in vitro wound repair model[102]
Skin transplantation	P2X7 blockade or deficiency prevents allogeneic skin transplant rejection[109]
Melanoma	ATP injection impairs A375 melanoma cell growth in immuno-compromised mice[120] P2X7 blockade inhibits B16 melanoma cell growth in immuno-competent mice[121,122] P2X7 deficiency impairs B16 melanoma cell migration in vitro[102] P2X7 deficiency in host leads to increased B16 melanoma growth and metastasis[102]
Basal cell carcinoma	ND
Squamous cell carcinoma	P2X7 deficiency in host enhances chemical-induced carcinogenesis[18] BzATP injection led to tumour apoptosis[18]

ATP: Adenosine triphosphate; BzATP: 2',3’-O-(4-benzoyl) benzoyl ATP; CHS: Contact hypersensitivity; IFN: Interferon; IL: Interleukin; ND: Not determined; TNF: Tumour necrosis factor.

Table 3 Roles of the P2X7 receptor in human skin diseases

Disease	Observations
Allergic contact dermatitis	Increased P2X7 expression in atopic dermatitis lesions[88]
Irritant contact dermatitis	ND
Psoriasis	Increased P2X7 expression in psoriatic skin lesions[30,88]
Cutaneous graft-vs-host disease	ND
Wound healing	P2X7 activation promotes VEGF release from monocytes[103]
Skin transplantation	ND
Melanoma	P2X7 is present on melanoma cells[117,118] and cell lines[119], with increased expression compared to normal melanocytes[119]
	P2X7 activation induces A375 melanoma[118] but suppresses HT168-M1 melanoma cell death[119]
Basal cell carcinoma	P2X7 is present in necrotic tumour centres and apoptotic tumour cells, and correlates inversely with tumour aggressiveness[123]
Squamous cell carcinoma	P2X7 is present in apoptotic tumour cells and its activation causes A431 SCC cell death[123]

ND: Not determined; SCC: Squamous cell carcinoma; VEGF: Vascular endothelial growth factor.