Update on the role of autophagy in systemic lupus erythematosus: A novel therapeutic target

Gao, Caina; Chen, Yanwen; Feng, Yuemin; Liu, Wei Jing; Liu, Huafeng

doi:10.1016/j.biopha.2015.02.017

Cited by 23 publications

(13 citation statements)

References 41 publications

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“…In contrast, p62 is a ubiquitin-binding autophagic receptor and signaling protein, the accumulation of which denotes autophagy-lysosomal pathway disruption, culminating in aggregates of autophagic vacuoles [33]. Our data confirmed increased LC3 and diminished p62 expression levels in PBMCs from patients with SLE, indicating excessive autophagic activation, consistent with previous reports contending for a pivotal role of autophagy in the abnormal activation of T cells in SLE sufferers, all supported by genetic, cell-biology, and model-animal studies [21,34,35]. Hence, we presumed that autophagy might be critical in Th17/Treg immune imbalances due to progressive SLE.…”

Section: Discussionsupporting

confidence: 90%

Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus

An¹,

Chen²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background: Imbalanced cellular immunity is critical to the pathogenesis of systemic lupus erythematosus (SLE). Recently, autophagy has emerged as a key homeostatic mechanism in T lymphocytes. This study was conducted to explore the impact of autophagy on the Th17/ regulatory T (Treg) immune imbalance in SLE. Methods: Peripheral Th17 and Treg cells from newly diagnosed patients with SLE and healthy controls were detected by flow cytometry. Additionally, the effects of chloroquine (CQ) autophagic inhibition on the Th17/Treg immune response were investigated in vitro. In addition, hydroxychloroquine (HCQ) treatment of the Th17/Treg immune response and the disease progression of lupus MRL/lpr mice were studied in vivo. Results: Compared with healthy controls, both peripheral Th17 and Treg cells of patients with SLE exhibited activated autophagy, resulting in a heightened Th17 proinflammatory response and diminished Treg immunosuppression. Furthermore, in vitro experiments indicated that CQ autophagic inhibition effectively rebalanced the Th17/Treg immune responses in patients with SLE. In vivo studies of MRL/lpr mice similarly confirmed that HCQ treatment decisively inhibited the autophagy of Th17/Treg cellular subsets, restoring the immune balance, lowering the serum levels of inflammatory cytokines and autoantibodies, and improving renal histopathology. Conclusion: Activated autophagy contributed to the Th17/Treg immune imbalance in SLE, and chloroquine autophagic inhibition rebalanced Th17/ Treg-mediated immunity and ameliorated SLE.N. An, Y. Chen and C. Wang contributed equally to this work.

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Section: Discussionsupporting

confidence: 90%

Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus

An¹,

Chen²,

Wang³

et al. 2017

Cell Physiol Biochem

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“…Our earlier work showed that macroautophagy, the best‐characterized type of autophagy, is abnormally enhanced in T lymphocytes from mice with lupus and patients with SLE . These results have been confirmed by others and supported by a recently completed study in B cells from (NZB × NZW)F1 mice and patients with lupus . Furthermore, macroautophagy was shown to be required for differentiation of plasmablasts and survival of memory B cells , thus indicating that this process seems to have a central role in humoral autoimmunity both in mice and in humans with lupus.…”

Section: Resultssupporting

confidence: 72%

Lupus Regulator Peptide P140 Represses B Cell Differentiation by Reducing HLA Class II Molecule Overexpression

Wilhelm

Wang

Schall

et al. 2018

Arthritis & Rheumatology

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These findings show that P140 down-regulates HLA class II overexpression in human lupus B cells, and also that P140 hampers the differentiation of B cells into autoantibody-secreting plasma cells, likely due to the resulting lack of T cell signaling and activation. This mechanism appears to switch off the downstream events leading to secretion of pathogenic autoantibodies, thus explaining the highly promising results obtained in clinical trials of P140 (Lupuzor) for the treatment of lupus.

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“…It has been known that macrophages mainly used in the innate immune response, whether the T-cells act in adaptive immune response [34]. The macrophage autophagy in lupus is one cause that might be considered as the leading caution of the insignificant IL-6 decrease [27,35]. It seems logical since the passive lupus manifestation still reveals the organ disorder, without severe inflammations occur.…”

Section: Il-6mentioning

confidence: 99%

The Benefits of Active Compounds in Kalanchoe Pinnata (Lmk) Pers Ethyl Acetate Fraction on Lupus Arthritis Mice

Indriyanti

Soeroso

Khotib

2017

Asian J Pharm Clin Res

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Objective: The aim of this research was to measure the effects of the ethyl acetate fraction of Kalanchoe pinnata (Lmk) Pers (EF-KP) on lupus arthritis mice. Methods:The research was performed by testing of CD123 + interferon-α (IFN-α + ) dendritic cells and CD68 + interleukin 6 (IL-6 + ) macrophages as the main biomarkers using flow cytometry method, and then, the outcomes were directly observed in the joint's tissue structure. The results of the research were analyzed using statistics. Results IL-6+ macrophages but not significantly. Finally, the outcome to the grade of joint damage was scored using Pritzker method. The treated groups have one grade lower, and the joint spaces were narrower than the untreated group. Conclusion:The results show the ability of the active compounds in EF-KP, which are comparable to 0.042 mg/kg of quercetin, to inhibit the progress of lupus arthritis pathogenesis in mice. It might reveals the effectiveness of the EF-KP in human with lupus arthritis. However, the further clinical research is necessary.

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Update on the role of autophagy in systemic lupus erythematosus: A novel therapeutic target

Cited by 23 publications

References 41 publications

Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus

Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus

Lupus Regulator Peptide P140 Represses B Cell Differentiation by Reducing HLA Class II Molecule Overexpression

The Benefits of Active Compounds in Kalanchoe Pinnata (Lmk) Pers Ethyl Acetate Fraction on Lupus Arthritis Mice

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