## 4 Neutrophils and Blood Transcriptome Signature in Soriasis  
Lesional skin biopsies are usually the ideal sample source to investigate psoriasis pathogenesis. Although less relevant to psoriasis, sampling blood has the advantage, over others, of allowing repetitive sampling with minimal risk or discomfort. Blood samples also provide information regarding the immune status of the patients. This blood transcriptome profiling offers the advantage of providing all such relevant information for not only psoriasis, but also other inflammatory disorders [75]. Most existing transcriptomic studies on psoriasis pathogenesis have focused on comparing skin biopsies from psoriasis patients and normal subjects [13; 31; 42]. However, there are few studies that have examined transcriptome changes in the blood. A significant increase of neutrophil numbers in psoriatic lesions is one of the histopathological hallmarks in psoriasis pathogenesis. The role played by neutrophils in psoriasis pathogenesis has received particular attention over recent years [76; 77; 75]. Evidence of neutrophil infiltration in lesional skin was earlier reported by [PERSON] et al. [47]. In the early phase of plaque formation, neutrophils infiltrate the dermis of the skin, then migrate to the epidermis and stratum corneum, where they accumulate as pustules or microabscesses [78; 79]. Blood transcriptome profiling from two public psoriasis data sets was studied by [PERSON] et al. [75]. This study found that there was a strong neutrophil-driven inflammation associated with blood transcripts of psoriasis patients. Such studies widen the possibility of assessing systemic inflammation in psoriasis. Moreover, blood transcripts are also relevant to assess markers of cardiovascular risk in psoriasis patients, since CVD is a common co-morbidity associated with psoriasis [75]. Peripheral blood of psoriatic patients exhibit two unique subsets of neutrophils (CD10\({}_{\text{pos}}\) and CD10\({}_{\text{neg}}\)) at different maturation stages. The number of CD10\({}_{\text{neg}}\) aged neutrophils was higher compared to number of CD\({}_{\text{pos}}\) neutrophils in psoriatic skin, since healthy skin is reported to have a smaller number of aged neutrophils [78]. These neutrophils are known to induce IL-17 production in T-cells in vitro, and, upon antibody treatment, the number decreased significantly. This highlights the regulatory effect of neutrophils in psoriatic skin [78]. The role of peripheral blood mononuclear cells (PBMCs) in psoriatic inflammation was studied by [PERSON] et al., who performed blood transcriptome analysis on samples from generalized pustular psoriasis (GPP) patients before and after acitretin treatment. It was found that low-density granulocytes accumulated in the PBMCs of psoriasis patients, and several genes involved in neutrophil recruitment and pattern recognition (FPR1, FPR2, etc.) were significantly down regulated [80]. Other downregulated transcripts included antimicrobial peptides (AMPs) S100A8, S100A9, and S100A12. All these results suggest the role of neutrophil activity in alleviation of GPP. A positive correlation between inflammasome signalling and psoriasis disease severity was investigated by [PERSON] et al. using blood transcriptome profiling from a cohort of 20 patients and 10 age-matched healthy controls [81]. Upregulation of inflammatory genes, including IL-19, suggested a linear relationship between differentially expressed inflammatory transcripts and disease severity. Endothelial transcriptome was assessed by collecting endothelial cells from psoriasis patients and healthy controls. This revealed significant upregulation of inflammatory transcripts, including IL-18, CXCL, CXCL10, VCAM-1, and CCL3. Taken together, this data indicates the link between psoriasis, inflammasome signalling, and impaired vascular health [81]. Recently, the same authors characterized the levels of PCSK9 and cardiovascular risk in the blood and skin of psoriatic patients [82].