P2X7 receptor involvement in the pathogenesis of Hidradenitis Suppurativa

The P2X7 receptor (P2X7R) is an ATP-gated plasma membrane ion channel widely distributed in human tissues, the highest expression being in cells of the immune and inflammatory systems, especially of the myeloid lineage [1]. The P2X7R plays different functions depending on the cell type and agonist concentration. One of the most relevant P2X7R activities consists in the regulation of inflammatory responses mainly through NLRP3 inflammasome activation and IL-1β processing and release [2]. Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent, painful nodules and abscesses of apocrine glands. Follicular occlusion and subsequent rupture are central events in HS. HS pathogenesis is not yet understood and many researches have recently focused on possible involvement of components of the immune system, mainly cytokines. Indeed, dysregulated cytokine expression, e.g. IL-1β, TNF-α, IL-6, was found in skin, plasma and immune cells of HS patients [3-6]. The aim of this study was to investigate a possible role of P2X7R in the pathogenesis of HS, also in view of a possible use of P2X7R antagonists in the treatment of this pathology with few options for effective therapy. For this 30 HS patients compared to 30 matched healthy control subjects, have been studied as regard skin biopsies, plasma and peripheral blood mononuclear cells (PBMC). Results show increased P2X7R expression in skin biopsies of HS patients respect to healthy controls (Fig. 1). Higher P2X7R immunostaining was shown by cheratinocytes as well as by some inflammatory cells in the derma, mainly macrophages and plasma cells. Plasma IL-1β levels were increased in HS patients respect to healthy controls suggesting a role for this cytokine in disease development. In apparent contrast with the last finding, PBMC from HS patients appeared defective in IL-1β release upon P2X7R stimulation. This is in agreement with deregulated and compartmentalized cytokine responses found by other authors [3,6]. Further research is necessary to identify the main source of circulating IL-1β as well as the expression of inflammasome components in HS lesional and possibly perilesional skin. Open image in new window Figure 1. Increased P2X7 immunostaining of skin section from HS patient (A) compared to control subject (B). 1. Bours MJ, Dagnelie PC, Giuliani AL, Wesselius A, Di Virgilio F (2011) P2 receptors and extracellular ATP: a novel homeostatic pathway in inflammation. Front Biosci (Schol Ed) 3:1443-1456. 2. Giuliani AL, Sarti AC, Falzoni S, Di Virgilio F (2017) The P2X7 receptor-interleukin-1 liaison. Front Pharmacol 8:123. 3. Kelly G, Hughes R, Mc Garry T, van den Born M, Adamzik K, Fitzgerald R, Lawlor C, Tobin AM, Sweeney CM, Kirby B (2015) Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol 173:1431-1439. 4. Xu H, Xiao X, He Y, Zhang X, Li C, Mao Q, Wu X, Wang B (2017) Increased serum interleuikin-6 levels in patients with hidradenitis suppurativa. Postepy Dermatol Alergol 34:82-84. 5. Van der Zee HH, de Ruiter L, van der Broecke DG, Dik WA, Laman JD, Pren EP (2011) Elevated levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol 164:1292-1298. 6. Kanni T, Tzanetakou V, Savva A, Kersten B, Pistiki A, van der Veerdonk FL, Netea MG, van der Meer J, Giamarellos-Bourboulis EJ (2015) Compartimentalized cytokine responses in hidradenitis suppurativa. PLoS One 10:e0130522.