Autophagy and autoimmunity

Wu, Dennis J.; Adamopoulos, Iannis E.

doi:10.1016/j.clim.2017.01.007

Cited by 110 publications

(68 citation statements)

References 93 publications

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“…These findings are in agreement with other studies that show WDFY3 is dispensable for starvation-induced autophagy [11]. WDFY3 targets specifically ubiquitinated protein aggregates in selective autophagy and has not been shown to play a role in other type of autophagy pathways such as LC3-associated phagocytosis [27]. …”

Section: Discussionsupporting

confidence: 92%

Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy

Adamopoulos

2017

Cellular Immunology

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WDFY3 is a master regulator of selective autophagy that we recently showed to interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in vivo via the NF-κB pathway. Since the NF-κB pathway plays a major role in inflammation herein, we investigate the role of WDFY3 in an arthritis animal model. Our data show that WDFY3 conditional knockout mice (Wdfy3loxP/loxP-LysM-Cre+,) were protected in the K/BxN serum transfer-induced arthritis animal model. These effects were independent of alterations in starvation-induced autophagy as evidenced by Western blot analysis of the autophagy marker LC3, autophagosome formation in osteoclast precursors and lysosome formation in osteoclasts derived from WDFY3-cKO mice compared to controls. Moreover, we demonstrate by immunofluorescence and co-immunoprecipitation that WDFY3 interacts with SQSTM1 in macrophages and osteoclasts. Collectively, our data suggest that loss of WDFY3 in myeloid cells leads to reduced severity of inflammatory arthritis independently of WDFY3 function in starvation-induced autophagy.

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Section: Discussionsupporting

confidence: 92%

Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy

Adamopoulos

2017

Cellular Immunology

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“…Previous studies have mainly focused on the muscular microenvironment ( 33 – 35 ); research on peripheral blood immune cells is lacking. T-cell homeostasis is disrupted in autoimmune diseases, including SLE and RA ( 36 , 37 ). Recent immunohistochemical studies on muscle biopsies from our laboratory and others have also demonstrated that T lymphocytes often infiltrate muscle fiber in PM/DM ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

Potential role of autophagy in T-cell survival in polymyositis and dermatomyositis

Shu

Chen

Peng

et al. 2017

Molecular Medicine Reports

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Peripheral blood T lymphocytopenia has previously been identified in polymyositis/dermatomyositis (PM/DM) patients. Therefore, the present study aimed to examine the potential role of autophagy in peripheral blood T cell survival in PM/DM patients. Transmission electron microscopy was used to detect the formation of autophagosomes of peripheral blood cluster of differentiation (CD)3+ T cells obtained from 24 patients with PM/DM and 21 healthy controls. Protein and mRNA expression levels of autophagy-related molecules were examined by western blot analysis and reverse transcription-quantitative polymerase chain reaction, respectively. The number of peripheral blood CD3+ T cells decreased significantly in PM/DM patients. The median percentage of apoptosis of CD3+ T cells in PM/DM patients was significantly increased compared with healthy controls. Furthermore, the number of autophagosomes and the expression of the autophagy markers microtubule-associated protein 1A/1B-light chain 3 (LC3) and Beclin-1 were significantly reduced in the circulating CD3+ T cells of PM/DM patients compared with those of healthy controls. LC3 and Beclin-1 protein levels correlated negatively with apoptosis rates in circulating CD3+ T cells in patients with PM/DM. CD3+ T cells from PM/DM patients treated with rapamycin increased autophagy and decreased apoptosis compared with untreated cells (P<0.05). In conclusion, these results suggested that autophagy may serve a potential protective role in the peripheral blood T cells of patients with PM/DM.

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“…The detailed interaction between inflammasomes and autophagy is beyond the scope of the article and described somewhere else . Autophagy and autophagy‐related gene polymorphisms are involved in various autoimmune diseases including IBD, SLE, RA, psoriasis, and MS . Genome‐wide association studies have shown an association between autophagy‐related gene 5 with SLE .…”

Section: Negative Regulation Of Cgas‐sting Signaling and Its Impact Omentioning

confidence: 99%

A STING to inflammation and autoimmunity

Kumar

2019

Journal of Leukocyte Biology

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Various intracellular pattern recognition receptors (PRRs) recognize cytosolic pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Cyclic GMP-AMP synthase (cGAS), a cytosolic PRR, recognizes cytosolic nucleic acids including dsDNAs. The recognition of dsDNA by cGAS generates cyclic GMP-AMP (GAMP). The cGAMP is then recognized by STING generating type 1 IFNs and NF-B-mediated generation of proinflammatory cytokines and molecules. Thus, cGAS-STING signaling mediated recognition of cytosolic dsDNA causing the induction of type 1 IFNs plays a crucial role in innate immunity against cytosolic pathogens, PAMPs, and DAMPs. The overactivation of this system may lead to the development of autoinflammation and autoimmune diseases. The article opens with the introduction of different PRRs involved in the intracellular recognition of dsDNA and gives a brief introduction of cGAS-STING signaling. The second section briefly describes cGAS as intracellular PRR required to recognize intracellular nucleic acids (dsDNA and CDNs) and the formation of cGAMP. The cGAMP acts as a second messenger to activate STING-and TANK-binding kinase 1-mediated generation of type 1 IFNs and the activation of NF-B. The third section of the article describes the role of cGAS-STING signaling in the induction of autoinflammation and various autoimmune diseases. The subsequent fourth section describes both chemical compounds developed and the endogenous negative regulators of cGAS-STING signaling required for its regulation. Therapeutic targeting of cGAS-STING signaling could offer new ways to treat inflammatory and autoimmune diseases. K E Y W O R D S

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Autophagy and autoimmunity

Cited by 110 publications

References 93 publications

Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy

Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy

Potential role of autophagy in T-cell survival in polymyositis and dermatomyositis

A STING to inflammation and autoimmunity

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