scholarly journals ATVB Distinguished Scientist Award

2017 ◽  
Vol 37 (5) ◽  
pp. 764-777 ◽  
Author(s):  
Klaus Ley ◽  
Norbert Gerdes ◽  
Holger Winkels
Keyword(s):  
Immune Cells ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Major Effect ◽  
Therapeutic Approaches ◽  
Cell Responses ◽  
Genetic Deletion ◽  
Antigen Presenting ◽  
Necrosis Factor

Objective— Immune cells play a critical role in atherosclerosis. Costimulatory and coinhibitory molecules of the tumor necrosis factor receptor and CD28 immunoglobulin superfamilies not only shape T-cell and B-cell responses but also have a major effect on antigen-presenting cells and nonimmune cells. Approach and Results— Pharmacological inhibition or activation of costimulatory and coinhibitory molecules and genetic deletion demonstrated their involvement in atherosclerosis. This review highlights recent advances in understanding how costimulatory and coinhibitory pathways shape the immune response in atherosclerosis. Conclusions— Insights gained from costimulatory and coinhibitory molecule function in atherosclerosis may inform future therapeutic approaches.

scholarly journals Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

2016 ◽  
Vol Volume 11 ◽  
pp. 1705-1712 ◽  
Author(s):  
Masaki Fujita ◽  
Ouchi Hiroshi ◽  
Satoshi Ikemage ◽  
Eiji Harada ◽  
Takemasa Matsumoto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Pulmonary Emphysema ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals A Critical Role of the p75 Tumor Necrosis Factor Receptor (p75TNF-R) in Organ Inflammation Independent of  TNF, Lymphotoxin α, or the p55TNF-R

1998 ◽  
Vol 188 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Eleni Douni ◽  
George Kollias
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Wide Range ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

scholarly journals Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Neil S. Lagali ◽  
Reza A. Badian ◽  
Xu Liu ◽  
Tobias R. Feldreich ◽  
Johan Ärnlöv ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dendritic Cell ◽  
Tumor Necrosis Factor ◽  
Corneal Epithelium ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Low Grade ◽  
Antigen Presenting ◽  
Necrosis Factor

AbstractType 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.

scholarly journals Different Activation of TRAF4 and TRAF6 in Inflammatory Bowel Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Shen ◽  
Yuqi Qiao ◽  
Zhihua Ran ◽  
Tianrong Wang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Cells ◽  
Bowel Disease ◽  
Binding Sites ◽  
Tumor Necrosis ◽  
Expression Patterns ◽  
Tumor Necrosis Factor Receptor ◽  
Inflammatory Bowel ◽  
Necrosis Factor ◽  
Comprehensive Study

In recent years, interests combining the exploration of tumor necrosis factor receptor-associated factor 4 (TRAF4) and TRAF6 in immune cells and transgenic mice are emerging. Although it has been found that TRAF4 and TRAF6 share the same TRAF binding sites, comprehensive study of TRAF4 and TRAF6 in inflammatory bowel disease (IBD) is still lacking. This paper shows similar and different expression patterns of TRAF4 and TRAF6 in patients with IBD. The results indicate that TRAF4 and TRAF6 are overexpressed in IBD. TRAF4 and TRAF6 play different roles in the pathogenesis of IBD. Moreover, TRAF4 may be an indicator of endoscopic disease activity of UC and TRAF6 preactivation can be detected in noninflamed colonic segments.

scholarly journals Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

2020 ◽  
Vol 21 (15) ◽  
pp. 5181
Author(s):  
Lisa K. Puntigam ◽  
Sandra S. Jeske ◽  
Marlies Götz ◽  
Jochen Greiner ◽  
Simon Laban ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Immune Checkpoints ◽  
Healthy Donors ◽  
Necrosis Factor

Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy.

scholarly journals Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 764 ◽  
Author(s):  
Lalita Subedi ◽  
Si Eun Lee ◽  
Syeda Madiha ◽  
Bhakta Prasad Gaire ◽  
Mirim Jin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Inflammatory Disorder ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear. TNF-α functions through its two main receptors: tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), also known as p55 and p75, respectively. Normally, the functions of soluble TNF-α-induced TNFR1 activation are reported to be pro-inflammatory and apoptotic. While TNF-α mediated TNFR2 activation has a dual role. Several synthetic drugs used as inhibitors of TNF-α for diverse inflammatory diseases possess serious adverse effects, which make patients and researchers turn their focus toward natural medicines, phytochemicals in particular. Phytochemicals targeting TNF-α can significantly improve disease conditions involving TNF-α with fewer side effects. Here, we reviewed known TNF-α inhibitors, as well as lately studied phytochemicals, with a role in inhibiting TNF-α itself, and TNF-α-mediated signaling in inflammatory diseases focusing mainly on CNS disorders.

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