Pei Qiao

Psoriasis is a chronic inflammatory skin condition driven by immune system dysfunction, genetic predisposition and environmental factors. Patients with psoriasis experience a well‐known clinical phenomenon of ‘winter severity and summer relief’, in which seasonal environmental factors play critical roles in the onset and progression of psoriasis. These factors include temperature, humidity, infection, light exposure and psychological stress. Seasonal changes in temperature and humidity can compromise skin barrier function and exacerbate inflammatory responses, thereby worsening psoriasis symptoms. Notably, during the winter, decreased light exposure leads to reduced vitamin D (VD) levels, reaching their lowest levels from late winter to early spring. This decline in VD levels is associated with increased disease activity, greater disease severity and more frequent flare‐ups in patients with psoriasis. During the winter, influenza and Streptococcus pneumoniae infections are more prevalent, which can further exacerbate psoriasis symptoms. Moreover, the environmental conditions in winter can trigger or intensify feelings of depression, which may adversely affect psoriasis through the brain–skin axis. In this comprehensive review, we thoroughly examined the influence of seasonal environmental factors on the incidence, recurrence and severity of psoriasis. By clarifying these complex relationships, we aimed to support the future development of more personalised and effective treatment and management strategies for patients with psoriasis.

Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4^hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4^lo neutrophils, CXCR4^hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4^hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4^hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4^hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4^hi neutrophil development and characterizes the contribution of CXCR4^hi neutrophils to vascular remodeling and inflammatory responses in skin.