Details

Autor(en) / Beteiligte

• Li, Ya-jun
• Zhou, Tao
• Zhang, Jing
• Zhang, Lei
• Ke, Hai
• Zhang, Cang
• Li, Ping

Titel

Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction

Ist Teil von

• Journal of ethnopharmacology, 2021-03, Vol.268, p.113551, Article 113551

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Psoriasis is a complex recurrent inflammatory skin disease with different pathological changes in different stages. Psoriasis in its active stage, which is comparable to the blood-heat type in traditional Chinese medicine (TCM), has been treated by Liangxue Jiedu Decoction (LJD) in TCM for decades, with proven efficacy. According to TCM theories, LJD has the function of removing heat and pathogenic factors from the blood. We aimed to investigate the molecular features associated with the active stage psoriasis and identify genes responding to LJD treatment accompanied by lesion remission. Healthy volunteers and psoriasis patients who met specific diagnostic criteria were recruited. Twenty-six transcriptomes were profiled from the peripheral blood mononuclear cells (PBMCs) of 10 psoriasis patients (pre- and post-treatment) and 6 healthy volunteers. RNA sequencing data were analyzed using an integrated approach combining differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA), by which gene expression was linked to multiple clinical traits, including psoriasis area and severity index (PASI), as well as the improvement rate of skin lesions (ΔPASI). The actions of LJD were then verified using an in vitro cell assay coupled to flow cytometric analysis and RT-PCR. We identified four network modules with statistical significance (P < 0.05), two of which connected to the PASI score, while the other two connected to 8-week treatment and ΔPASI, respectively. In psoriasis patients, activated inflammatory pathways and inhibited G-protein signaling genes (GTPase IMAP family member and G protein-coupled receptor) co-occurred, with high expression of CD83 and CD69, and low expression of CD160 and CD180, compared with the health. Accompanying LJD treatment and lesion remission, the expression of CD69 and cell cycle-related genes, including CCNA2, CCNB2, CDK1, and TOP2A, was down-regulated. The inhibitory role of LJD on CD69 expression was confirmed by the decline of activating naïve CD4+ T lymphocytes. Our study suggests that active psoriasis is characterized by unbalanced immune status with dendrite cell and lymphocyte-associated inflammatory activation as well as NK cell- and B cell-associated defense response aberrance. LJD played an inhibitory role in T cell activation, a process located downstream pathological cascade of psoriasis. [Display omitted] •Application of clinical trait-connected WGCNA to discover disease-associated molecular features and treatment response genes.•Activated inflammatory pathways and suppressed defensive responses co-exist in active psoriasis.•Inhibition of CD69 expression in T cell activation is one of the therapeutic mechanisms of LJD.•An immune network transformation model of LJD treatment during the remission of active psoriasis is proposed.