Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

Abstract

Accumulating epidemiologic evidence has revealed that metabolic syndrome is an independent risk factor for psoriasis development and is associated with more severe psoriasis. Adiponectin, primarily recognized as a metabolic mediator of insulin sensitivity, has been newly drawing attention as a mediator of immune responses. Here we demonstrate that adiponectin regulates skin inflammation, especially IL-17-related psoriasiform dermatitis. Mice with adiponectin deficiency show severe psoriasiform skin inflammation with enhanced infiltration of IL-17-producing dermal Vg4 þ gd-T cells. Adiponectin directly acts on murine dermal gd-T cells to suppress IL-17 synthesis via AdipoR1. We furthermore demonstrate here that the adiponectin level of skin tissue as well as subcutaneous fat is decreased in psoriasis patients. IL-17 production from human CD4-or CD8-positive T cells is also suppressed by adiponectin. Our data provide a regulatory role of adiponectin in skin inflammation, which would imply a mechanism underlying the relationship between psoriasis and metabolic disorders.

Adiponectin Signaling Regulates Lipid Production in Human Sebocytes

“…Serum adiponectin levels are decreased in patients with psoriasis, and its levels are inversely correlated to the severity of disease and concomitant diseases such as metabolic syndrome [19, 20]. In addition, adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells [21]. Low adiponectin levels were associated with increased prevalence of atopic dermatitis and its aggravation was associated with changes in the plasma concentration of adiponectin [22, 23].…”

Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin

“…IL-17A is a potent amplifier of ongoing inflammation, which plays an important role in the progression of chronic inflammation and autoimmunity [2]. Recently, ApN has been found to suppress IL-17A production from T cells, thereby attenuating psoriasiform skin inflammation [36]. This suppressive effect is of importance in our own study since muscle IL-17A mRNA levels have been reported to be higher in DMD than that in non-DMD subjects and to be associated with the clinical outcome of the patients [37].…”

Effects of secukinumab on serum adipocytokines: preliminary data

“…Increased levels of cells that produce IL-17 are found in the circulation, joints, and skin plaques of patients with psoriatic arthritis (12). Finally, some data seem to suggest that adipocytokines could also act by interfering with IL-17 axis (3,13,14). For these reasons we decided to evaluate the possible interferences of secukinumab on different adipocytokines.…”

“…Chronic inflammation in Pso and PsA can partially explain the development of atherosclerosis and CV diseases, but also the concomitant alterations in the glucose metabolism (diabetes and insulin resistance) and lipids (dyslipidaemia) enhance this risk (2). Systemic inflammation induced by obesity and metabolic syndrome could exacerbate local inflammation, worsening both Pso and PsA (3). Indeed, increasing evidence is suggesting that metabolic syndrome is an independent risk factor for Pso development and is associated with more severe forms of Pso (3).…”

“…Systemic inflammation induced by obesity and metabolic syndrome could exacerbate local inflammation, worsening both Pso and PsA (3). Indeed, increasing evidence is suggesting that metabolic syndrome is an independent risk factor for Pso development and is associated with more severe forms of Pso (3). Nowadays, adipose tissue is considered as an active endocrine and immune organ, producing various cytokines, named adipocytokines, and they link together inflammation and metabolic disorders (4).…”