CD74 Deficiency Mitigates Systemic Lupus Erythematosus–like Autoimmunity and Pathological Findings in Mice

Zhou, Yi; Liu, Li; Yu, Xueqing; Sukhova, Galina K.; Zhang, Lijun; Kyttaris, Vasileios C.; Tsokos, George C.; Stillman, Isaac E.; Ichimura, Takaharu; Bonventre, Joseph V.; Libby, Peter; Shi, Guo‐Ping

doi:10.4049/jimmunol.1600028

Cited by 18 publications

(18 citation statements)

References 90 publications

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“…Both MIF and CD74 elevated expression positively correlated with worsening inflammation. MIF inhibition and CD74 deficiency protected against glomerulonephritis in lupusprone mice (110,111). Despite these results that suggest MIF-CD74 pathway plays a role in lupus pathology, a phase 1 clinical trial of an anti-MIF monoclonal antibody in lupus nephritis was terminated early for unclear reasons (112).…”

Section: Proinflammatory Effects and Disease Outcomes Linked To Mif-cmentioning

confidence: 99%

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

2020

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Wound healing after an injury is essential for life. An in-depth understanding of the healing process is necessary to ultimately improve the currently limited treatment options for patients suffering as a result of damage to various organs and tissues. Injuries, even the most minor, trigger an inflammatory response that protects the host and activates repair pathways. In recent years, substantial progress has been made in delineating the mechanisms by which inflammatory cytokines and their receptors facilitate tissue repair and regeneration. This mini review focuses on emerging literature on the role of the cytokine macrophage migration inhibitory factor (MIF) and its cell membrane receptor CD74, in protecting against injury and promoting healing in different parts of the body.

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Section: Proinflammatory Effects and Disease Outcomes Linked To Mif-cmentioning

confidence: 99%

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

2020

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“…The proteolytic cleavage of Ii is catalyzed by active CTSS and other proteases [41]. The CLIP fragment is then cleaved, translocated to the plasma membrane of the antigen-presenting cell to ultimately activate CD4+ T cells [41,42]. CTSS-mediated cleavage of li is not only important for presentation but also mediates dendritic cell motility [41,42].…”

Section: Ctss Functionsmentioning

confidence: 99%

“…The CLIP fragment is then cleaved, translocated to the plasma membrane of the antigen-presenting cell to ultimately activate CD4+ T cells [41,42]. CTSS-mediated cleavage of li is not only important for presentation but also mediates dendritic cell motility [41,42]. CTSS has also been found to be crucial in regulating toll-like receptor (TLR) 9 signaling.…”

Section: Ctss Functionsmentioning

confidence: 99%

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

et al. 2020

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Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment. Proteases in pulmonary diseases Research in the last 60 years has demonstrated that proteases are critical contributors to pulmonary disease pathophysiology. Initially known as protein-degrading enzymes with a restricted spectrum of substrates, recent studies have revealed that the diversity of protease substrates and biological effects triggered by their processing is vast [1, 2]. Proteases are primarily known for their matrix degradation capabilities, but also play significant roles in other biological mechanisms such as angiogenesis, growth factor bioavailability, cytokine processing, receptor shedding and activation, as well as cellular processes including migration, proliferation, invasion, and survival [3]. Importantly, protease activity requires tight regulation, and disruption of the close interplay between proteases, substrates and inhibitors may contribute to the pathogenesis and progression of a variety of pulmonary diseases, including muco-inflammatory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), as well as infection [4]. In pulmonary diseases with a high neutrophil burden such as CF, a protease:antiprotease imbalance is frequently observed. The activity of proteases such as neutrophil elastase (NE) in the respiratory tract is regulated by antiproteases, such as α1-antitrypsin (A1AT) [5], secretory leukoprotease inhibitor (SLPI) [6] and elafin [7]. However, in diseases like CF, the antiproteases are overburdened by their cognate proteases and this imbalance can result in chronic airway inflammation, decreased mucociliary clearance, mucus obstruction, extracellular matrix (ECM) remodeling, increased susceptibility to infection and impaired immune responses [8].

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“…In addition to autoimmune disease, CD74 plays a role in renal tubular epithelial cells. CD74 de ciency not only reduced lupus-like autoimmunity, but also reduced renal pathology in chronic graft-versus-host mice [55]. In addition, CD74 knockout also reduced the surface expression of MHC class II and severely attenuated Th2 response, but the Th1 response was relatively preserved.…”

Section: Discussionmentioning

confidence: 93%

Quantitative proteomic analysis and identification of differentially expressed proteins involved in blast exposure-induced inflammatory response

Liu¹,

Tong

Cong

et al. 2020

Preprint

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Abstract Background Previous studies found that blast injury caused a significant increased expression of interleukin-1, IL-6 and tumor necrosis factor, a significant decrease in the expression of IL-10, an increase in Evans blue leakage, and a significant increase in inflammatory cell infiltration in the lungs. However, the molecular characteristics of lung injury at different time points after blast exposure have not yet been reported. Therefore, in this study, tandem mass spectrometry (TMT) quantitative proteomics and bioinformatics analysis were used for the first time to gain a deeper understanding of the molecular mechanism of lung blast injury at different time points. Methods Fourty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h and 1 w after low-intensity blast exposure. TMT quantitative proteomics and bioinformatics analysis were performed to analyze protein expression profiling in the lungs from control and blast-exposed mice, and differential protein expression was verified by Western blotting. Results The results demonstrated that blast exposure induced severe lung injury, leukocyte infiltration, and the production of inflammatory factors in mice. After analyzing the expression changes in global proteins and inflammation-related proteomes after blast exposure, the results showed that a total of 6,861 global proteins and 608 differentially expressed proteins were identified, of which 215, 128, 187, 232, and 65 proteins were identified at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. Moreover, blast exposure-induced 177 differentially expressed proteins were associated with inflammatory responses, which were enriched in the inflammatory response regulation, leukocyte transendothelial migration, phagocytosis, and immune response. Conclusions Therefore, blast exposure may induce early inflammatory response of lung tissue by regulating the expression of key proteins in the inflammatory process, suggesting that early inflammatory response may be the initiating factor of lung blast injury. These data can provide potential therapeutic candidates or approaches for the development of future treatment of lung blast injury.

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CD74 Deficiency Mitigates Systemic Lupus Erythematosus–like Autoimmunity and Pathological Findings in Mice

Cited by 18 publications

References 90 publications

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Quantitative proteomic analysis and identification of differentially expressed proteins involved in blast exposure-induced inflammatory response

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