Psoriasis
Dysregulation of Akt-FOXO1 Pathway Leads to Dysfunction of Regulatory T Cells in Patients with Psoriasis
Psoriasis is a T lymphocyte–driven systemic inflammatory disease. Regulatory T cells (Tregs) are essential for establishing and maintaining immune tolerance. In this study, we found that patients with psoriasis and healthy controls had comparable percentages of circulating CD4+CD25+FOXP3+ Tregs, but psoriatic Tregs had reduced suppressive function. Thereafter, mRNA arrays were performed to study the gene expression profile of psoriatic Tregs. Psoriatic Tregs expressed high levels of a T helper type 1–like transcription factor and cytokines such as T-bet and IFN-γ.Potentiation of Psoriasis-Like Inflammation by PCSK9
Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, therefore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment.Extracellular ATP and IL-23 Form a Local Inflammatory Circuit Leading to the Development of a Neutrophil-Dependent Psoriasiform Dermatitis
Psoriasis is a chronic inflammatory skin disease dependent on the IL-23/IL-17 axis, a potent inflammatory pathway involved in pathogen clearance and autoimmunity. Several triggers have been proposed as initiators for psoriasis, including alarmins such as adenosine triphosphate. However, the role of alarmins in psoriasis pathogenesis and cutaneous inflammation has not been well addressed. Studies show that signaling through the P2X7 receptor (P2X7R) pathway underlies the development of psoriasiform inflammation.CARD14 Gain-of-Function Mutation Alone Is Sufficient to Drive IL-23/IL-17–Mediated Psoriasiform Skin Inflammation In Vivo
Rare autosomal dominant mutations in the gene encoding the keratinocyte signaling molecule CARD14, have been associated with an increased susceptibility to psoriasis, but the physiological impact of CARD14 gain-of-function mutations remains to be fully determined in vivo. Here, we report that heterozygous mice harboring a CARD14 gain-of-function mutation (Card14ΔE138) spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis, and immune cell infiltration.
