Corrigendum: Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

[This corrects the article DOI: 10.3389/fphar.2022.972397.].

Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

Hydroxychloroquine (HCQ) is derivative of the heterocyclic aromatic compound quinoline, which has been used for the treatment of autoimmune diseases. The central purpose of this study was to investigate therapeutic effects and inflammatory immunological molecular mechanism of HCQ in experimental autoimmune hepatitis (AIH). Treatment with HCQ ameliorated hepatic pathologic damage, inflammatory infiltration, while promoted regulatory T cell (Treg) and down-regulated CD8+T cell differentiation in AIH mice induced by S-100 antigen. In vitro, HCQ also suppressed pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-12) secretion, promoted anti-inflammatory cytokine (TGF-ß1) secretion. HCQ mainly impaired T cell lipid metabolism but not glycolysis to promote Treg differentiation and function. Mechanistically, HCQ down-regulated GRK2 membrane translocation in T cells, inhibited GRK2-PI3K interaction to reduce the PI3K recruiting to the membrane, followed by suppressing the phosphorylation of PI3K-AKT-mTOR signal. Pretreating T cells with paroxetine, a GRK2 inhibitor, disturbed HCQ effect to T cells. HCQ also reversed the activation of the PI3K-AKT axis by 740 Y-P (PI3K agonist). Meanwhile, HCQ inhibited the PI3K-AKT-mTOR, JAK2-STAT3-SOCS3 and increased the AMPK signals in the liver and T cells of AIH mice. In conclusion, HCQ exhibited specific and potent therapeutic effects on AIH and attendant liver injury, which was attributed to HCQ acted on GRK2 translocation, inhibited metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 signal in T lymphocytes, thereby modulating lipid metabolism of T cell function to regulate Treg differentiation and function.

Plasma Long Non-Coding RNA Expression Profiles in Patients with Rheumatoid Arthritis.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. METHODS: The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. RESULTS: Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. CONCLUSIONS: We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.

The clinical value of hematological markers in rheumatoid arthritis patients treated with tocilizumab.

BACKGROUND: Emerging evidence indicates that some hematological markers have critical value in evaluating treatment response. This study was performed to determine the clinical value of hemoglobin (Hb), platelet (Plt), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: Fifty-two RA patients receiving TCZ were recruited and followed for 6 months. The values of abovementioned hematological markers were collected. Clinical disease activity index (CDAI) and disease activity score based on 28 joints (DAS28)-ESR were calculated. Correlation analysis was conducted by calculating Pearson's correlation coefficient. The change in disease activity between groups according to the baseline level of hematological markers was compared by t test. RESULTS: Significant correlation between change in NLR (△NLR), change in PLR (△PLR), and change in CDAI (△CDAI) was found (△NLR: r = 0.30, P = 0.03; △PLR: r = 0.31, P = 0.03). The change in Plt (△Plt) was correlated with change in DAS28-ESR (△DAS28-ESR) (r = 0.36, P = 8.24 × 10-3 ). Greater improvement in CDAI was seen in patients categorized into Plt high group (t = 2.06, P = 0.04), NLR high group (t = 2.15, P = 0.04), and PLR high group (t = 2.41, P = 0.02) compared with the contrast group. CONCLUSION: Our study demonstrated that △Plt, △NLR, and △PLR could be used to monitor the clinical response to TCZ. RA patients with high baseline levels of Plt, NLR, and PLR achieved more improvement, indicating these hematological markers might be utilized to guide TCZ treatment.

Asymmetric Construction of Pyrrolidines Bearing a Trifluoromethylated Quaternary Stereogenic Center via Cu(I) -Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with ß-CF3 -ß,ß-Disubstituted Nitroalkenes.

A direct and convenient method has been developed for the synthesis of optically active pyrrolidines bearing a quaternary stereogenic center containing a CF3 group at the C-3 position of the pyrrolidine ring. The synthesis system, Cu(I) /Si-FOXAP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with ß-CF3 -ß,ß-disubstituted nitroalkenes, provides pyrrolidines with high diastereoselectivities (up to >98:2 d.r.) and excellent enantioselectivities (up to >99.9 ee) and performs well for a broad scope of substrates under mild conditions.