Weight loss improves inflammation by T helper 17 cells in an obese patient with psoriasis at high risk for cardiovascular events

Despite the abundance of epidemiological evidence for the high comorbid rate between psoriasis and obesity, systematic approaches on common in ammatory mechanisms have not been adequately explored. We performed a meta-analysis of publicly available RNA-sequencing datasets to unveil putative mechanisms that are postulated to exacerbate both diseases, utilizing both late-stage, disease-speci c meta-analyses and consensus gene co-expression network (cWGCNA). Single-gene meta-analyses reported several common in ammatory mechanisms fostered by the perturbed expression pro le of pathogenic cell types. Assessment of gene overlaps between both diseases revealed signi cant overlaps between up-(n = 170, P-value = 6.07×10 -65 ) and down-regulated (n = 49, P-value = 7.1×10 − 7 ) genes, associated with increased T cell response and activated transcription factors. Our cWGCNA approach disentangled 48 consensus modules, associated with either the differentiation of leukocytes or metabolic pathways with similar correlation signals in both diseases. Notably, all our analyses con rmed the association of the perturbed T helper (Th)17 differentiation pathway in both diseases. Our novel ndings through whole transcriptomic analyses characterize the in ammatory commonalities between psoriasis and obesity implying the assessment of several expression pro les that could serve as putative comorbid disease progression biomarkers and therapeutic interventions.

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Causal effects of lipid‐lowering drugs on inflammatory skin diseases: Evidence from drug target Mendelian randomisation

Zang,

Li,

Zhang

et al. 2024

Experimental Dermatology

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Clinical research has revealed that inflammatory skin diseases are associated with dyslipidaemia. Modulating lipids is also a rising potential treatment option. However, there is heterogeneity in the existing evidence and a lack of large‐scale clinical trials. Observational research is prone to bias, making it difficult to determine causality. This study aimed to evaluate the causal association between lipid‐lowering drugs and inflammatory skin diseases. A drug target Mendelian randomisation (MR) analysis was conducted. Genetic targets of lipid‐lowering drugs, including proprotein convertase subtilis kexin 9 (PCSK9) and 3‐hydroxy‐3‐methylglutaryl‐assisted enzyme A reductase (HMGCR) inhibitor, were screened. Common inflammatory skin diseases, including psoriasis, allergic urticaria, rosacea, atopic dermatitis, systemic sclerosis and seborrhoeic dermatitis, were considered as outcomes. Gene‐predicted inhibition of PCSK9 was causally associated with a decreased risk of psoriasis (ORIVW [95%CI] = 0.600 [0.474–0.761], p = 2.48 × 10−5) and atopic dermatitis (ORIVW [95%CI] = 0.781 [0.633–0.964], p = 2.17 × 10−2). Gene‐predicted inhibition of HMGCR decreased the risk of seborrhoeic dermatitis (ORIVW [95%CI] = 0.407 [0.168–0.984], p = 4.61 × 10−2) but increased the risk of allergic urticaria (ORIVW [95%CI] = 3.421 [1.374–8.520], p = 8.24 × 10−3) and rosacea (ORIVW [95%CI] = 3.132 [1.260–7.786], p = 1.40 × 10−2). Among all causal associations, only PCSK9 inhibition demonstrated a robust causal effect on psoriasis after a more rigorous Bonferroni test (p < 4.17 × 10−3, which is 0.05/12). Modulating lipids via PCSK9 inhibition may offer potential therapeutic targets for psoriasis and atopic dermatitis. Given the potential cutaneous side effects associated with HMGCR inhibitors, PCSK9 inhibitors could be considered viable alternatives in lipid‐lowering medication.

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Weight loss improves inflammation by T helper 17 cells in an obese patient with psoriasis at high risk for cardiovascular events

Cited by 3 publications

References 10 publications

Identification and characterization of circulating and adipose tissue infiltrated CD20+ T cells from subjects with obesity that undergo bariatric surgery

Identification and characterization of circulating and adipose tissue infiltrated CD20+ T cells from subjects with obesity that undergo bariatric surgery

Transcriptomic meta-analysis characterizes molecular commonalities between psoriasis and obesity

Causal effects of lipid‐lowering drugs on inflammatory skin diseases: Evidence from drug target Mendelian randomisation

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