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

Abstract

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 of IL-23 and IL-23R have been found in human atherosclerotic plaque, and levels correlated with symptom duration and mortality. Also, upregulation of IL-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 of IL-23/IL-17 have also been observed and available data support a synergistic role of IL-23/IL-17 in b-cells damage. In obesity, signs of an expansion of Th17 subset in adipose tissue have been reported, as well as elevated concentrations of IL-23 in obese patients. In non-alcoholic fatty liver disease, closely related to metabolic syndrome, but also in other mentioned cardiometabolic disorders, a predominance of IL-23 and other related proinflammatory factors has been identified as participating in their pathogenesis. Thus, the involvement of the IL-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.

Osteopontin Serum Concentration and Metabolic Syndrome in Male Psoriatic Patients

“…In the course of Ps, increased triglycerides, LDL cholesterol and decreased HDL cholesterol values are the most frequently observed lipid disturbances [1,2]. In our study, the levels of total CHOL and TG as well as CHOL/HDL and TG/HDL ratios were significantly higher in Ps patients than in HVs, while LDL-CHOL did not differ between both groups.…”

Psoriasis and Cardiovascular Risk: A Comprehensive Review

“…On the other hand, some authors described that the risk of psoriasis being increased in the obese population, and this clinical scenario may negatively affect systemic treatment of psoriasis [21].…”

Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis

“…Recent studies revealed that metabolic disorders, including abdominal obesity and serum dyslipidemia, were positively correlated with psoriasis risk 9 , 10 due to their “low-grade chronic inflammatory state” involving the IL-23/Th17 axis 6 . Psoriasis has been identified as a risk factor for metabolic diseases 6 , and increasing evidence provides support for this epidemiological observation. For example, increased IL-23 and IL-17 levels were found in diabetes, suggesting their synergistic role in β-cell damage 7 .…”

“…Evidence indicates that TNF-α and IL-1β facilitate insulin resistance development by elevating blood insulin and HDL cholesterol levels 3 and insulin resistance suppresses keratinocyte differentiation, resulting in persistent proliferation 4 . Moreover, the IL-23/Th17 axis has the diabetogenic potential 5 , and psoriasis has been identified as a risk factor for metabolic diseases due to shared pathogenic pathways, including the IL-23/Th17 axis 6 - 8 .…”