**1. Introduction**

Psoriasis (Ps) is a chronic inflammatory T-cell mediated disease, that is manifested mainly as skin lesions and extracutaneous comorbidities, the overall symptomatology of the disease having a strong impact on the patients' life quality [1].

Worldwide, the prevalence of this disease is increasing for both adults and children, and varies between 0.09% and 11.4%, respectively between 1.5% and 5% in most developed countries. The disease incidence depends on age, sex, ethnicity, geographical regions, and environmental factors [2]. Ps especially affects Caucasians as compared to other ethnic groups and is more common in high-income countries. In children, the incidence increases with age, the median age at diagnosis being 10.6 years, with a higher prevalence in girls compared to boys [3].

The exact causes of Ps onset are still unknown. Ps is a complex and multifactorial skin condition that occurs on an altered genetic and immunologic background, favored by environmental factors [4] and aggravated by extrinsic risk factors and intrinsic risk factors [5].

Its complexity rides also on the fact that Ps presents a wide spectrum of skin lesions therefore, the specific clinical type of Ps is important in choosing the adequate treatment protocol. Ps is histologically characterized by keratinocytes (KCs) hyperproliferation which induces acanthosis, elongation of the rete ridges, hyperkeratosis, and parakeratosis, and an inflammatory infiltrate consisting mainly of dendritic cells (DCs) and T cells [6].

For many years, Ps was classified as an immune-mediated inflammatory disorder and less as an autoimmune condition due to the fact that the autoantigens causing T cell activation remain unknown. Recent studies reported the identification of four possible autoantigens involved in Ps' pathogenesis: KCs – derived antimicrobial peptide LL-37 (cathelicidin) [7], ADAMTS-like-protein 5 (a disintegrin- and metalloprotease domain-containing thrombospondin type 1 motif-like 5) produced by melanocytes, lipid antigens generated by phospholipase A2 group IVD (PLA2G4D) [8] and keratin 17 derived from hair follicles [9]. Studies regarding the autoimmune character of Ps have also focused on the existence of specific autoantibodies, the most common being anti-stratum corneum antibodies [10] and anti-heat shock protein 65 [11]. However, the clinical significance of these autoantibodies remains still evasive.

Although Ps is recognized as one of the most prevalent T-cell mediated chronic inflammatory skin conditions, its pathogenesis involved both innate and adaptive immune cells. Pathogenic crosstalk between hyper-proliferative resident KCs and immune cells mediated by immune and non-immune molecules are responsible for the development and maintenance of Ps' inflammatory state [12].

Two phases were described in the Ps' pathogenesis: initiation of psoriatic events, in which the cells belonging to the innate immunity (DCs, NK cells, Mɸ-macrophages) play an important role, and the phase of maintaining inflammatory status, in which the key players belong to the adaptive immunity (T helper (h)-cell subsets). In earlier stages of the disease, under the action of triggering factors (genetic, environmental, physical injury, infections, stress), KCs and cells belonging to innate immunity (plasmacytoid (P) DCs, NK cells, Mɸ) produce tumor necrosis factor (TNF)-α, interferon (IFN)-α, IFN-β, IFN-γ, interleukin (IL)-1β, IL-6 thus activating the myeloid (M)DCs. In the initiation of psoriatic events, a starting key is represented by the activation of PDCs, secreting two type I IFNs (IFN-α, IFN-β), further promoting MDCs activation. Activated MDCs, by secreting IL-12 and IL-23, will determine the differentiation of naïve T-cells into Th1, Th17, and Th22 subpopulations. TNF-α, IFN-γ, IL-17, and IL-22 secreted by these effector subsets, will be able to activate KCs, which will produce a variety of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-19, IL-36), chemokines (CXCL1/2/3/5/8), antimicrobial peptides (LL-37) and S100 proteins, thus propagating and maintaining the inflammatory status [13–15]. A general outline of the initiation and propagation stages of Ps is depicted in **Figure 1**.

Ps in not only a skin disease, it also has significant disabling systemic manifestations [13]. The disease is frequently associated with arthritic, metabolic, cardiovascular, and psychological comorbidities, which can lead to increased mortality among affected persons [16]. Knowing and understanding the relationship between Ps and other associated pathologies is particularly important for optimal clinical management of patients.

Depending on the Ps severity, there is a wide range of therapeutic options, from the traditional topical treatment, phototherapy, and systemic treatments, to new biological therapies. Despite various treatment options available, Ps still remains an incurable and undertreated disease [17], and finding an adjuvant treatment [18] to help existing ones remains a challenge for researchers.

#### *Immune Markers in Psoriasis DOI: http://dx.doi.org/10.5772/intechopen.102567*

#### **Figure 1.**

*Immune mechanisms are associated with the onset of psoriatic events and the maintenance of the inflammatory status. KCs and innate immune cells are activated by triggers that secrete cytokines, leading to the differentiation in Th1, Th17, and Th22 cells via IL-12, IL-23, and TNF-α secreted by activated MDCs. These effectors promote KCs activation through TNF-α, IFN-γ, IL17, and IL22, leading to the perpetuation of the inflammatory cycle by generating AMP (LL-37, β-defensins, S100 proteins) and by secreting of cytokines (TNF-α, IL-6, IL-1β) and chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL8, CXCL9, CXCL10, CXCL20). Created with BioRender.com.*

Although it is unequivocally accepted that Ps is a T-cell mediated condition, both innate and specific immune cells are highly involved in the pathogenesis of Ps. The aberrant interactions between immune cells and resident hyper-proliferative KCs are mediated by immune and non-immune related molecules which lead to amplification of the local immune responses, that maintain the chronic inflammatory status. In this chapter, we will highlight the immune molecules resident in the psoriatic tissue or appending to the blood circulation that can indicate the prognosis of this systemic autoimmune disease. Moreover, we will focus on immune cells resident or circulating ones that can pinpoint the clinical evolution of the psoriatic disease. All these data can be developed in immune markers patterns that aid Ps' diagnosis and/or future (immune)therapies development.
