Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis

Qi, Yuanyuan; Zhou, Xu‐jie; Cheng, Fajuan; Hou, Ping; Ren, Yali; Wang, Suxia; Zhao, Ming‐Hui; Yang, Li; Martinez, Jennifer; Zhang, Hong

doi:10.1136/annrheumdis-2018-213028

Cited by 87 publications

(75 citation statements)

References 64 publications

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“…Intensification of autophagy in podocytes might originate from stress in the glomerulus caused by deposited immune complexes or local inflammatory cytokines and activating autophagy via ROS production or mTORC1 inhibition . Notably, autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury . This reinforces the notion that both aberrant systemic immunity and intrarenal immunopathology contribute to lupus nephritis, in which autophagy may exert an important effect.…”

Section: Renal Impairmentsupporting

confidence: 63%

“…Future comprehensive studies are needed in renal cell cultures, human kidney tissues, and experimental animal models to elucidate the role of renal resident cells autophagy in the pathogenesis of lupus nephritis (LN). Our recent data indicated that autophagy was increased in kidney tissue from lupus prone MRL lpr/lpr mice with nephritis, compared with MRL lpr/lpr mice without nephritis or C57BL6/J mice [98]. Autophagosomes were observed in podocytes from MRL lpr/lpr mice with nephritis and in human patients with LN.…”

Section: Renal Impairmentmentioning

confidence: 90%

“…Our recent data indicated that autophagy was increased in kidney tissue from lupus prone MRL lpr/lpr mice with nephritis, compared with MRL lpr/lpr mice without nephritis or C57BL6/J mice . Autophagosomes were observed in podocytes from MRL lpr/lpr mice with nephritis and in human patients with LN.…”

Section: Renal Impairmentmentioning

confidence: 91%

“…Autophagosomes were observed in podocytes from MRL lpr/lpr mice with nephritis and in human patients with LN. Intensification of autophagy in podocytes might originate from stress in the glomerulus caused by deposited immune complexes or local inflammatory cytokines and activating autophagy via ROS production or mTORC1 inhibition . Notably, autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury .…”

Section: Renal Impairmentmentioning

confidence: 99%

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Autophagy and immunological aberrations in systemic lupus erythematosus

Zhou

Zhang

2019

Eur J Immunol

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease, in which immune defects can occur at multiple points of the cascading auto‐aggressive immune reactions, resulting in a striking heterogeneity of clinical presentations. The clinical manifestations of such autoimmune response can be severe: common manifestations symptoms include rash and renal inflammation progressing to kidney failure. Autophagy, the cellular “self‐digestion” process, is a key factor in the interplay between innate and adaptive immunity. Dysregulation of autophagy has been implicated in numerous autoimmune diseases. Several lines of evidence from genomic studies, cell culture systems, animal models, and human patients are emerging to support the role of autophagy in progression and pathogenesis of SLE. In this review, we summarize recent key findings on the aberrations of autophagy in SLE, with a special focus on how deregulated autophagy promotes autoimmunity and renal damage. We will also discuss how the observed findings may be translated into therapeutic settings.

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Section: Renal Impairmentsupporting

confidence: 63%

Section: Renal Impairmentmentioning

confidence: 90%

Section: Renal Impairmentmentioning

confidence: 91%

Section: Renal Impairmentmentioning

confidence: 99%

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Autophagy and immunological aberrations in systemic lupus erythematosus

Zhou

Zhang

2019

Eur J Immunol

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“…In its phosphorylated form, NRBF2 inhibits autophagy, while promoting it in its unphosphorylated form . Intact autophagy, in turn, was recently reported to confer protection against autoimmune disorders such as lupus nephritis . Thus, one could speculate that NRBF2 autoantibodies may have a protective role against damage acquisition by inhibiting NRBF2 phosphorylation and thereby promoting autophagy.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Vordenbäumen

Brinks

Hoyer

et al. 2019

Arthritis & Rheumatology

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Objective. To investigate the role of epitope spreading in established systemic lupus erythematosus (SLE). Methods. IgG autoantibody reactivity with 398 distinct recombinant proteins was measured over a period of 6 years in 69 SLE patients and compared to that in 45 controls. Changes in mean fluorescence intensity (MFI), number of autoantibodies to distinct antigens, and reactivity with distinct clones of established antigenic targets (e.g., U1 RNP, Sm, and ribosomal P) representing epitope fine mapping were assessed. Linear mixed modeling, adjusted with Bonferroni correction for age and sex, was applied.Results. The total number of autoantibodies, mean MFI, and number of autoantibodies in epitope fine mapping were higher in SLE patients compared to controls (P < 0.0001). The total number of antibodies to distinct autoantigens remained stable over time, while the mean MFI decreased over time in SLE (P < 0.021). SLE patients showed variable recognition of epitopes in fine mapping over time. In particular, in SLE patients, more clones of the U1 RNP complex were recognized at the time of new organ involvement (+0.65) (P = 0.007). Mean MFI was higher in patients with lupus nephritis (P = 0.047). The time-averaged MFIs of 22 individual autoantibodies (including double-stranded DNA [dsDNA]) were higher, after Bonferroni correction, in SLE (P < 0.0001). The MFIs of dsDNA and histone cluster 2 H3c were associated with scores on the Systemic Lupus Activity Measure (P < 0.0001).Conclusion. Longitudinal surveillance of the IgG autoantibody repertoire in established SLE reveals evidence of sustained breadth of autoantibody repertoire without significant expansion. Associations of disease activity with dsDNA and with histone H3 autoantibodies were confirmed.

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Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

Zhang,

Du,

Jin

et al. 2023

Advanced Science

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Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4+ T cells and loss of immune tolerance. However, the involvement of CD8+ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single‐cell RNA sequencing. This is observed that CD8+CD27+CXCR3− T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8+CD27+CXCR3− T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin‐2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score‐related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8+CD27+CXCR3− T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.

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Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis

Abstract: Podocyte autophagy is activated in lupus-prone mice and patients with lupus nephritis. Increased autophagy is cytoprotective against antibody and interferon-α induced podocyte injury.

Cited by 87 publications

References 64 publications

Autophagy and immunological aberrations in systemic lupus erythematosus

Autophagy and immunological aberrations in systemic lupus erythematosus

Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

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Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis

Abstract: Podocyte autophagy is activated in lupus-prone mice and patients with lupus nephritis. Increased autophagy is cytoprotective against antibody and interferon-α induced podocyte injury.

Cited by 87 publications

References 64 publications

Autophagy and immunological aberrations in systemic lupus erythematosus

Autophagy and immunological aberrations in systemic lupus erythematosus

Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Identification and Characterization of CD8+CD27+CXCR3− T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

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Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus