The role of the interleukin-23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis

Alterations in the innate and adaptive immunity underpin psoriasis pathophysiology, with the Th17 cells subset now recognized as the fundamental cells in the key controlling pathway involved in its pathogenesis. Since psoriasis is a systemic disease with important comorbidity, further knowledge on the interleukin (IL)-23/Th17 axis led to the hypothesis that there may be shared pathogenic pathways between primary skin disease and comorbidity. Psoriasis has been identified as a risk factor for cardiovascular and metabolic disease, and increasing evidence gives support to this epidemiological observation from the clinical-pathologically field. As an example, increased levels ofIL-23 andIL-23R have been found in human atherosclerotic plaque, and levels correlated with symptom duration and mortality. Also, upregulation ofIL-23/IL-17 seems to play an important role in both myocardial damage and stroke, with interesting reports on deleterious effect neutralization after administration of related anti-bodies in both associated conditions. In diabetic patients, increased levels ofIL-23/IL-17 have also been observed and available data support a synergistic role ofIL-23/IL-17 in beta-cells damage. In obesity, signs of an expansion of Th17 subset in adipose tissue have been reported, as well as elevated concentrations ofIL-23 in obese patients. In non-alcoholic fatty liver disease, closely related to metabolic syndrome, but also in other mentioned cardiometabolic disorders, a predominance ofIL-23 and other related pro-inflammatory factors has been identified as participating in their pathogenesis. Thus, the involvement of theIL-23/Th17 axis in these shared psoriasis-cardiometabolic pathogenic mechanisms is reviewed and discussed in the light of the existing preclinical and clinical evidence, including that from comorbid psoriasis patients.