# Soriasis and Seasonality: Exploring the Genetic and Epigenetic Interactions
## 4 Environmental Factors Affecting Psoriasis
### Air Pollution  
Particulate matter (PM\({}_{2.5}\): \(\leq\)2.5 \(\upmu\)m; PM\({}_{10}\): \(\leq\)10 \(\upmu\)m) and nitrogen dioxide (NO\({}_{2}\)) cause oxidative damage to the epithelial cells by production of volatile organic compounds, increasing TEWL [113; 130; 131; 132]. According to the available data, PM\({}_{2.5}\), PM\({}_{10}\), and surface ozone (O\({}_{3}\)) may play essential roles in psoriasis development via aryl hydrocarbon receptor (AHR) activation, leading to increased Th-17 differentiation [133; 134; 135; 136]. AHR is a ligand-dependent transcriptional factor that plays a crucial role in Th\({}_{17}\) functioning, influencing the production of IL-22 and taking part in chemical sensing of the circadian rhythm and the skin's adaptive response to environmental stimuli by controlling the T\({}_{\text{reg}}\) and Th\({}_{17}\) cell differentiation [113; 132; 134; 137; 133]. This ligand regulates the T\({}_{\text{reg}}\) and Th\({}_{17}\) cell differentiation, playing a vital role in the development of psoriasis. The AHR is modulated by the novel drug, tapinarof, which was recently approved by the FDA in the topical treatment for psoriasis [138]. Other outdoor pollutants such as carbon monoxide (CO) and sulfur dioxide (SO\({}_{2}\)) also cause epidermal damage due to ROSs [113; 139]. Air pollutants present seasonal distribution [140; 141]. It was shown that increased concentrations of air pollutants cause flares of PsV [142; 143]. [PERSON] et al. [143] reported that the blood concentration of cadmium was statistically significantly higher in patients with psoriasis and correlated with the disease severity.  
Air pollution may influence psoriasis flare-ups due to its seasonal pattern caused by indoor heating and decrease beneficial UV exposure for psoriatic patients [113; 144].  
Another air pollutant, cigarette smoke, is strongly associated with the incidence and severity of psoriasis [145; 133]. Nicotine causes an increased secretion of proinflammatory cytokines IL-2, IL-12, IFN-\(\gamma\), and granulocyte-monocyte colony-stimulating factor, which also participate in the keratinocyte's differentiation [146]. [PERSON] et al. [147] showed that CD1a\({}^{+}\) antigen-presenting cells (APCs) from the lungs of patients with emphysema could induce autoreactive, pathological T helper 1 (Th\({}_{1}\)) and Th\({}_{17}\) cell responses and cause overexpression for IFN-\(\gamma\) and IL-17A, which play a crucial role in psoriasis pathogenesis. Smoking is also related to two single nucleotide polymorphisms at the _CSMD1_ gene (rs7007032 and rs10088247), which effect epithelial cell turnover and influence the differentiation of keratinocytes [39].  
PsV patients have an increased risk of pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and pulmonary hypertension [148]. Similarly, pulmonary disorders, such as COPD [149; 150], asthma [151], and OSA [152], are related to the higher risk of psoriasis susceptibility. Smoking is also strongly associated with psoriasis [153]. [PERSON] et al. [154] conducted a meta-analysis of the relationship between smoking and treatment efficacy in PsV patients. The authors concluded that smoking negatively affects the efficacy of psoriasis treatment and smokers are exposed to more immune regulators compared to non-smokers. These results indicate that smoking causes worse improvement than conventional and biological treatments. Onthe other hand, smoking is associated with an increased incidence of psoriasisform lesions in inflammatory bowel disease patients undergoing anti-TNF therapy [155].