scholarly journals Thymic stromal lymphopoietin: master switch for allergic inflammation

2006 ◽  
Vol 203 (2) ◽  
pp. 269-273 ◽  
Author(s):  
Yong-Jun Liu
Keyword(s):  
Atopic Dermatitis ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Allergic Inflammation ◽  
Skin Lesions ◽  
Thymic Stromal Lymphopoietin ◽  
Dendritic Cell Activation

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL) 7–like cytokine that triggers dendritic cell–mediated T helper (Th)2 inflammatory responses. TSLP is highly expressed by keratinocytes in skin lesions of patients with atopic dermatitis and is associated with dendritic cell activation in situ, suggesting that TSLP might be a master switch for allergic inflammation at the epithelial cell–dendritic cell interface. New reports now establish a direct link between TSLP expression and the pathogenesis of atopic dermatitis and asthma in vivo, and begin to reveal the molecular mechanisms underlying TSLP-induced allergic inflammation.

scholarly journals Enhancing anti-melanoma immunity by electrochemotherapy and in vivo dendritic-cell activation

2012 ◽  
Vol 1 (9) ◽  
pp. 1655-1657 ◽  
Author(s):  
Gianni Gerlini ◽  
Paola Di Gennaro ◽  
Lorenzo Borgognoni
Keyword(s):  
Dendritic Cell ◽  
Cell Activation ◽  
Dendritic Cell Activation

scholarly journals IL-10 Receptor Signaling Empowers Regulatory T Cells to Control Th17 Responses and Protect from GN

2018 ◽  
Vol 29 (7) ◽  
pp. 1825-1837 ◽  
Author(s):  
Paul Diefenhardt ◽  
Anna Nosko ◽  
Malte A. Kluger ◽  
Johannes V. Richter ◽  
Claudia Wegscheid ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Th17 Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Receptor Signaling ◽  
Dendritic Cell Activation ◽  
Fluorescent Reporter

Background Th17 cells are central pathogenic mediators of autoimmune disease, including many forms of GN. IL-10 receptor signaling (IL-10R) in regulatory T cells (Tregs) has been implicated in the downregulation of Th17 cells, but the underlying molecular mechanisms and functional relevance of this process remain unclear.Methods We generated mice with Treg-specific IL-10Ra deficiency and subjected these mice to nephrotoxic serum–induced nephritis as a model of crescentic GN. Immune responses and Treg phenotypes were extensively analyzed.Results Compared with controls, mice with IL-10Ra−/− Tregs showed a spontaneously overshooting Th17 immune response. This hyper-Th17 phenotype was further boosted during GN and associated with aggravated renal injury. Notably, abrogation of IL-10Ra signaling in Tregs increased dendritic cell activation and production of Th17-inducing cytokines. In contrast, Treg trafficking and expression of chemokine receptor CCR6 remained unaffected, indicating mechanisms of Th17 control, differing from those of previously identified CCR6+ Treg17 cells. Indeed, the capacity for direct in vitro suppression of Th17 responses by IL-10Ra−/− Tregs was significantly impaired. As underlying pathology, analyses conducted in vitro and in vivo using double-fluorescent reporter mice revealed strikingly decreased IL-10 production by IL-10Ra−/− Tregs. To assess, whether reduced IL-10 could explain the hyper Th17 phenotype, competitive cotransfer experiments were performed. Supporting our concept, IL-10Ra−/− T cells differentiated into Th17 cells at much higher frequencies than wild type T cells did during GN.Conclusions IL-10R engagement optimizes Treg-mediated suppression of Th17 immunity. We hypothesize a feed-forward loop, in which IL-10Ra signaling reinforces IL-10 secretion by Tregs which potently controls Th17 development via direct and indirect mechanisms. IL-10R thus may be a promising therapeutic target for the treatment of GN.

MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits dendritic cell activation and prevents autoimmunity as shown in vivo using the EAE model

Immunobiology ◽  
2008 ◽  
Vol 212 (9-10) ◽  
pp. 839-853 ◽  
Author(s):  
Brigitte Horstmann ◽  
Elisabeth Zinser ◽  
Nadine Turza ◽  
Franz Kerek ◽  
Alexander Steinkasserer
Keyword(s):  
Dendritic Cell ◽  
Natural Product ◽  
Cell Activation ◽  
Dendritic Cell Activation ◽  
Eae Model

scholarly journals Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

2017 ◽  
Vol 1 (9) ◽  
pp. 557-568 ◽  
Author(s):  
Maria Dolores Lopez Robles ◽  
Annaick Pallier ◽  
Virginie Huchet ◽  
Laetitia Le Texier ◽  
Severine Remy ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cell Surface ◽  
Human Blood ◽  
Cell Activation ◽  
Inhibitory Receptor ◽  
Dendritic Cell Activation ◽  
Key Points ◽  
T Cell Priming

Key PointsCLEC-1 is restricted to CD16− myeloid DCs in human blood and acts as an inhibitory receptor to restrain downstream Th17 activation. CLEC-1–deficient rats highlight an in vivo function for CLEC-1 in preventing excessive T-cell priming and effector Th responses.

scholarly journals Serine Lipids of Porphyromonas gingivalis Are Human and Mouse Toll-Like Receptor 2 Ligands

2013 ◽  
Vol 81 (9) ◽  
pp. 3479-3489 ◽  
Author(s):  
Robert B. Clark ◽  
Jorge L. Cervantes ◽  
Mark W. Maciejewski ◽  
Vahid Farrokhi ◽  
Reza Nemati ◽  
...  
Keyword(s):  
Cell Activation ◽  
Inflammatory Responses ◽  
Periodontal Pathogen ◽  
Toll Like Receptor ◽  
Dendritic Cell Activation ◽  
Content Type ◽  
Hek Cells ◽  
Toll Like Receptor 2

ABSTRACTThe total cellular lipids ofPorphyromas gingivalis, a known periodontal pathogen, were previously shown to promote dendritic cell activation and inhibition of osteoblasts through engagement of Toll-like receptor 2 (TLR2). The purpose of the present investigation was to fractionate all lipids ofP. gingivalisand define which lipid classes account for the TLR2 engagement, based on bothin vitrohuman cell assays andin vivostudies in mice. Specific serine-containing lipids ofP. gingivalis, called lipid 654 and lipid 430, were identified in specific high-performance liquid chromatography fractions as the TLR2-activating lipids. The structures of these lipids were defined using tandem mass spectrometry and nuclear magnetic resonance methods.In vitro, both lipid 654 and lipid 430 activated TLR2-expressing HEK cells, and this activation was inhibited by anti-TLR2 antibody. In contrast, TLR4-expressing HEK cells failed to be activated by either lipid 654 or lipid 430. Wild-type (WT) or TLR2-deficient (TLR2−/−) mice were injected with either lipid 654 or lipid 430, and the effects on serum levels of the chemokine CCL2 were measured 4 h later. Administration of either lipid 654 or lipid 430 to WT mice resulted in a significant increase in serum CCL2 levels; in contrast, the administration of lipid 654 or lipid 430 to TLR2−/−mice resulted in no increase in serum CCL2. These results thus identify a new class of TLR2 ligands that are produced byP. gingivalisthat likely play a significant role in mediating inflammatory responses both at periodontal sites and, potentially, in other tissues where these lipids might accumulate.

scholarly journals CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Enhao Li ◽  
Xiaobao Yang ◽  
Yuzhang Du ◽  
Guanzheng Wang ◽  
David W. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Suppressor Cells ◽  
The Cancer Genome Atlas ◽  
Dendritic Cell Activation ◽  
Antitumor Effects ◽  
Activation Markers

Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.

scholarly journals Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis

2020 ◽  
Author(s):  
Katsuhiro Togami ◽  
Sun Sook Chung ◽  
Vikas Madan ◽  
Christopher M. Kenyon ◽  
Lucia Cabal-Hierro ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
X Chromosome ◽  
Rna Splicing ◽  
Cell Activation ◽  
Intron Retention ◽  
Plasmacytoid Dendritic Cell ◽  
Sex Bias ◽  
Loss Of Function ◽  
Dendritic Cell Activation

ABSTRACTBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of plasmacytoid dendritic cells (pDCs). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics of primary BPDCN and modeling disease-associated mutations, we link acquired alterations in RNA splicing to abnormal pDC development and inflammatory response through Toll-like receptors. Loss-of-function mutations in ZRSR2, an X chromosome gene encoding a splicing factor, are enriched in BPDCN and nearly all mutations occur in males. ZRSR2 mutation impairs pDC activation and apoptosis after inflammatory stimuli, associated with intron retention and inability to upregulate the transcription factor IRF7. In vivo, BPDCN-associated mutations promote pDC expansion and signatures of decreased activation. These data support a model in which male-biased mutations in hematopoietic progenitors alter pDC function and confer protection from apoptosis, which may impair immunity and predispose to leukemic transformation.STATEMENT OF SIGNIFICANCESex bias in cancer is well recognized but the underlying mechanisms are incompletely defined. We connect X chromosome mutations in ZRSR2 to an extremely male-predominant leukemia. Aberrant RNA splicing induced by ZRSR2 mutation impairs dendritic cell inflammatory signaling, interferon production, and apoptosis, revealing a sex- and lineage-related tumor suppressor pathway.

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