Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4 + helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

Abbreviations: BMD, bone mineral density; BMI, body mass index; CI, confidence interval; DEXA, dual-energy X-ray absorptiometry; HR, hazard ratio; LMR, lymphocyte-to-monocyte ratio; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; NLR, neutrophil-to-lymphocyte ratio; OR, odds ratio; PDW, platelet distribution width; PLR, platelet-to-lymphocyte ratio; PMOP, postmenopausal osteoporosis; RDW, red blood cell distribution width; SII, systemic immune-inflammation index. AbstractBackground: Postmenopausal osteoporosis (PMOP) is a bone metabolism disorder involving systematic inflammation activation. Blood routine examination is easily available in clinical practice and contains abundant information reflecting the systematic inflammation level. Thus, it is attractive to achieve early diagnosis of PMOP and predict osteoporotic fracture risk just based on the biomarkers in blood routine examination.Methods: A multi-centric prospective cohort study was designed and enrolled postmenopausal women from two independent institutions. All participants underwent the dual-energy X-ray absorptiometry (DEXA) scanning for diagnosing PMOP. Blood routine examination was conducted, and the key inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) were calculated. PMOP patients were followed up to observe osteoporotic fracture and identify the related risk predictors.Results: A total of 92 participants out of 238 enrolled postmenopausal women were diagnosed with PMOP, with a prevalence of 38.66%. The main risk factors identified for PMOP included older age (OR = 2.06, 95% CI = 1.14-3.72), longer menopause duration (OR = 3.14, 95% CI = 2.06-4.79), higher NLR (OR = 2.11, 95% CI = 1.37-3.25), and higher SII (OR = 3.02, 95% CI = 1.98-4.61). Besides age and menopause duration, SII ≥834.89 was newly identified as a prominent risk factor for discriminating osteoporotic fracture risk in PMOP patients (HR = 3.66, 95% CI = 1.249-10.71). Conclusion:As an easy and economical biomarker calculated from blood routine examination, SII not only acts as a good risk predictor for PMOP diagnosis but also well discriminates the osteoporotic fracture risk, which deserves further investigation and application in clinical practice.

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Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-B pathway, subsequently affecting the expression of NF-B target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism.Methods: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague-Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-B inhibitor BAY 11-7082.Results: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-B in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-B pathway, subsequently upregulating pro-inflammatory factors and MMPs. Conclusions:Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-B pathway.typical pathological signatures of AAA include inflammatory infiltration in the adventitia and tunica media, aortic elastin proteolytic degradation, and pathological remodeling 4) . Vascular inflammation has been regarded as the primary determinant of AAA 5) . It proceeds with gradual infiltration of many inflammatory cell types, including macrophages, lymphocytes, mast cells, and neutrophils, into the intima from the adven-Copyright©2019 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.