Insights into interplay of immunopathophysiological events and molecular mechanistic cascades in psoriasis and its associated comorbidities

Psoriasis is an inflammatory skin disease with complex pathogenesis and multiple etiological factors. Besides the essential role of autoreactive T cells and constellation of cytokines, the discovery of IL-23/Th17 axis as a central signaling pathway has unraveled the mechanism of accelerated inflammation in psoriasis. This has provided insights into psoriasis pathogenesis and revolutionized the development of effective biological therapies. Moreover, genome-wide association studies have identified several candidate genes and susceptibility loci associated with this disease. Although involvement of cellular innate and adaptive immune responses and dysregulation of immune cells have been implicated in psoriasis initiation and maintenance, there is still a lack of unifying mechanism for understanding the pathogenesis of this disease. Emerging evidence suggests that psoriasis is a high-mortality disease with additional burden of comorbidities, which adversely affects the treatment response and overall quality of life of patients. Furthermore, changing trends of psoriasis-associated comorbidities and shared patterns of genetic susceptibility, risk factors and pathophysiological mechanisms manifest psoriasis as a multifactorial systemic disease. This review highlights the recent progress in understanding the crucial role of different immune cells, proinflammatory cytokines and microRNAs in psoriasis pathogenesis. In addition, we comprehensively discuss the involvement of various complex signaling pathways and their interplay with immune cell markers to comprehend the underlying pathophysiological mechanism, which may lead to exploration of new therapeutic targets and development of novel treatment strategies to reduce the disastrous nature of psoriasis and associated comorbidities. •Psoriasis is a momentous health challenge affecting more than 125 million people globally.•IL-23/Th17 axis provided insights into immunological interactions and cytokines constellation in psoriasis.•Despite the role of immune responses and dysregulated immune cells, psoriasis lacks a unifying mechanism of pathogenesis.•Multifactorial pathophysiology and additional comorbidities present psoriasis as a systemic disease.•Understanding the interplay of complex signaling pathways in psoriasis-related comorbidities is important.