scholarly journals CD73+ Dendritic Cells in Cascading Th17 Responses of Experimental Autoimmune Uveitis-Induced Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
MinHee K. Ko ◽  
Hui Shao ◽  
Henry J. Kaplan ◽  
Deming Sun
Keyword(s):  
Dendritic Cells ◽  
Critical Role ◽  
Γδ T Cells ◽  
Adenosine Monophosphate ◽  
Toll Like Receptor ◽  
Promoting Effect ◽  
Receptor Ligand ◽  
Antigen Presenting ◽  
Different Levels ◽  
Experimental Autoimmune

Previous studies have shown that CD73 is pivotal in the conversion of pro-inflammatory adenosine triphosphate into anti-inflammatory adenosine and that immune cells of the same type that express different levels of CD73 are functionally distinct. In this study we show that adenosine enhances the Th17 promoting effect of dendritic cells (DCs), and DCs expressing CD73 critically augment Th17 responses. Bone marrow dendritic cells (BMDCs) do not constantly express CD73; however, a significant portion of the BMDCs expressed CD73 after exposure to Toll-like receptor ligand, leading to stronger Th17 responses by converting adenosine monophosphate to adenosine. We show that the CD73+ BMDCs play a critical role in cascading Th17 responses, and CD73+ BMDCs are functionally augmented after treatment with Toll-like receptor ligand. Splenic antigen presenting cells (DCs) of CD73−/− mouse have a poor Th17-stimulating effect, even after exposure to lipopolysaccharide (LPS) or γδ T cells, indicating that induction of CD73+ DCs is critically involved in augmented Th17 responses. We conclude that CD73+ DCs critically trigger cascading Th17 responses, and the activated Th17 cells that express CD73 further augment Th17 responses, leading to cascading exacerbation. Hence, disabling the CD73 function of DCs should block this cascading response and mitigate Th17 responses.

Plasmacytoid dendritic cells and autoimmune inflammation

2014 ◽  
Vol 395 (3) ◽  
pp. 335-346 ◽  
Author(s):  
Georgina Galicia ◽  
Jennifer L. Gommerman
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Toll Like Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Abstract Plasmacytoid dendritic cells (pDC) are a sub-population of dendritic cells (DC) that produce large amounts of type I interferon (IFN) in response to nucleic acids that bind and activate toll-like-receptor (TLR)9 and TLR7. Type I IFN can regulate the function of B, T, DC, and natural killer (NK) cells and can also alter the residence time of leukocytes within lymph nodes. Activated pDC can also function as antigen presenting cells (APC) and have the potential to prime and differentiate T cells into regulatory or inflammatory effector cells, depending on the context. In this review we discuss pDC ontogeny, function, trafficking, and activation. We will also examine how pDC can potentially be involved in regulating immune responses in the periphery as well as within the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).

scholarly journals Dendritic Cells and Cancer: From Biology to Therapeutic Intervention

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 521 ◽  
Author(s):  
Wylie ◽  
Macri ◽  
Mintern ◽  
Waithman
Keyword(s):  
Dendritic Cells ◽  
Tumor Immunity ◽  
Critical Role ◽  
Cancer Therapies ◽  
Local Immunity ◽  
Dc Function ◽  
T Cell Infiltration ◽  
Anti Cancer ◽  
Heterogenous Population ◽  
Antigen Presenting

Inducing effective anti-tumor immunity has become a major therapeutic strategy against cancer. Dendritic cells (DC) are a heterogenous population of antigen presenting cells that infiltrate tumors. While DC play a critical role in the priming and maintenance of local immunity, their functions are often diminished, or suppressed, by factors encountered in the tumor microenvironment. Furthermore, DC populations with immunosuppressive activities are also recruited to tumors, limiting T cell infiltration and promoting tumor growth. Anti-cancer therapies can impact the function of tumor-associated DC and/or alter their phenotype. Therefore, the design of effective anti-cancer therapies for clinical translation should consider how best to boost tumor-associated DC function to drive anti-tumor immunity. In this review, we discuss the different subsets of tumor-infiltrating DC and their role in anti-tumor immunity. Moreover, we describe strategies to enhance DC function within tumors and harness these cells for effective tumor immunotherapy.

scholarly journals Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by a Retrovirus

2004 ◽  
Vol 78 (2) ◽  
pp. 576-584 ◽  
Author(s):  
Dalia Burzyn ◽  
John C. Rassa ◽  
David Kim ◽  
Irene Nepomnaschy ◽  
Susan R. Ross ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Virus Binding ◽  
Toll Like Receptor 4 ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Mouse mammary tumor virus (MMTV) is a milk-borne retrovirus that exploits the adaptive immune system. It has recently been shown that MMTV activates B cells via Toll-like receptor 4 (TLR4), a molecule involved in innate immune responses. Here, we show that direct virus binding to TLR4 induced maturation of bone marrow-derived dendritic cells and up-regulated expression of the MMTV entry receptor (CD71) on these cells. In vivo, MMTV increased the number of dendritic cells in neonatal Peyer's patches and their expression of CD71; both these effects were dependent on TLR4. Thus, retroviral signaling through TLRs plays a critical role in dendritic-cell participation during infection.

scholarly journals miR29a and miR378b Influence CpG-Stimulated Dendritic Cells and Regulate cGAS/STING Pathway

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 197 ◽  
Author(s):  
Abid Ullah Shah ◽  
Yanan Cao ◽  
Naila Siddique ◽  
Jian Lin ◽  
Qian Yang
Keyword(s):  
Dendritic Cells ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Mouse Bone Marrow ◽  
Cytokine Detection ◽  
Sting Pathway ◽  
Factor Α ◽  
Antigen Presenting ◽  
And Control

The Cytosine–phosphate–guanosine (CpG) motif, which is specifically recognized intracellularly by dendritic cells (DCs), plays a crucial role in regulating the innate immune response. MicroRNAs (miRNAs) can strongly influence the antigen-presenting ability of DCs. In this study, we examine the action of miRNAs on CpG-stimulated and control DCs, as well as their effect on cyclic guanosine monophosphate-adenosine monophosphate (GMP–AMP) synthase (cGAS) and the stimulator of interferon genes (STING) signal pathway. Firstly, we selected miRNAs (miR-29a and miR-378b) based on expression in CpG-stimulated mouse bone marrow-derived dendritic cells (BMDCs). Secondly, we investigated the functions of miR-29a and miR-378b on CpG-stimulated and unstimulated BMDCs. The results showed that miR-29a and miR-378b increased expression of both the immunoregulatory DC surface markers (CD86 and CD40) and the immunosuppressive molecule CD273 by DCs. Thirdly, cytokine detection revealed that both miR-29a and miR-378b enhanced interferon-β (IFN-β) expression while suppressing tumor necrosis factor-α (TNF-α) production. Finally, our results suggest that miR-378b can bind TANK-binding kinase binding protein 1 (TBKBP1) to activate the cGAS/STING signaling pathway. By contrast, miR-29a targeted interferon regulatory factor 7 (IRF7) and promoted the expression of STING. Together, our results provide insight into the molecular mechanism of miRNA induction by CpG to regulate DC function.

scholarly journals Dendritic Cells in Sepsis: Pathological Alterations and Therapeutic Implications

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Dong-Dong Wu ◽  
Tao Li ◽  
Xin-Ying Ji
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Wnt Signaling Pathway ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Innate And Adaptive Immunity ◽  
Therapeutic Implications ◽  
Surface Molecules ◽  
Antigen Presenting

Sepsis is the leading cause of death for critically ill patients in recent years. Dendritic cells (DCs) are important antigen-presenting cells and play a key role in immune response by regulating the innate and adaptive immunity. The number of DCs, the differentiation of monocytes into DCs, and the levels of surface molecules associated with the function of DCs are changed in the development of sepsis. There are many mechanisms involved in the alterations of DCs during sepsis, including the induction of apoptosis, reactive oxygen species generation, activation of the Wnt signaling pathway, epigenetic regulation, and variation in Toll-like receptor-dependent signaling. In this review, we present the classifications of DC subsets and mechanisms involved in the alterations of DCs in sepsis, as well as further discuss the therapeutic strategies targeting DCs in sepsis to improve the aberrant immune response and prolong the life during sepsis progression.

scholarly journals C-Reactive Protein Suppresses the Th17 Response Indirectly by Attenuating the Antigen Presentation Ability of Monocyte Derived Dendritic Cells in Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhi-Yuan Shen ◽  
Yi Zheng ◽  
Maggie K. Pecsok ◽  
Ke Wang ◽  
Wei Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Blood Monocytes ◽  
C Reactive Protein ◽  
Autoimmune Encephalomyelitis ◽  
Th17 Response ◽  
Reactive Protein ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is a classical murine model for Multiple Sclerosis (MS), a human autoimmune disease characterized by Th1 and Th17 responses. Numerous studies have reported that C-reactive protein (CRP) mitigates EAE severity, but studies on the relevant pathologic mechanisms are insufficient. Our previous study found that CRP suppresses Th1 response directly by receptor binding on naïve T cells; however, we did not observe the effect on Th17 response at that time; thus it remains unclear whether CRP could regulate Th17 response. In this study, we verified the downregulation of Th17 response by a single-dose CRP injection in MOG-immunized EAE mice in vivo while the direct and indirect effects of CRP on Th17 response were differentiated by comparing its actions on isolated CD4+ T cells and splenocytes in vitro, respectively. Moreover, the immune cell composition was examined in the blood and CNS (Central Nervous System), and a blood (monocytes) to CNS (dendritic cells) infiltration pathway is established in the course of EAE development. The infiltrated monocyte derived DCs (moDCs) were proved to be the only candidate antigen presenting cells to execute CRP’s function. Conversely, the decrease of Th17 responses caused by CRP disappeared in the above in vivo and in vitro studies with FcγR2B−/− mice, indicating that FcγR2B expressed on moDCs mediates CRP function. Furthermore, peripheral blood monocytes were isolated and induced to establish moDCs, which were used to demonstrate that the antigen presenting ability of moDCs was attenuated by CRP through FcγR2B, and then NF-κB and ERK signaling pathways were manifested to be involved in this regulation. Ultimately, we perfected and enriched the mechanism studies of CRP in EAE remission, so we are more convinced that CRP plays a key role in protecting against EAE development, which may be a potential therapeutic target for the treatment of MS in human.

scholarly journals Streptococcus pneumoniae Infection Aggravates Experimental Autoimmune Encephalomyelitis via Toll-Like Receptor 2

2006 ◽  
Vol 74 (8) ◽  
pp. 4841-4848 ◽  
Author(s):  
Isabel Herrmann ◽  
Markus Kellert ◽  
Hauke Schmidt ◽  
Alexander Mildner ◽  
Uwe K. Hanisch ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Interleukin 6 ◽  
T Cell Response ◽  
Respiratory Pathogen ◽  
Toll Like Receptor ◽  
Tissue Destruction ◽  
Autoimmune Encephalomyelitis ◽  
Toll Like Receptor 2 ◽  
Experimental Autoimmune

ABSTRACT The course of autoimmune inflammatory diseases of the central nervous system (CNS) can be influenced by infections. Here we assessed the disease-modulating effects of the most frequent respiratory pathogen Streptococcus pneumonia on the course of experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) peptide, challenged intraperitoneally with live S. pneumoniae type 3, and then treated with ceftriaxone. EAE was monitored by a clinical score for 35 days after immunization. EAE was unaltered in mice infected with S. pneumoniae 2 days before and 21 days after the first MOG35-55 injection but was more severe in animals infected 7 days after the first MOG35-55 injection. The antigen-driven systemic T-cell response was unaltered, and the intraspinal Th1 cytokine mRNA concentrations at the peak of disease were unchanged. The composition of CNS-infiltrating cells and subsequent tissue destruction were only slightly increased after S. pneumoniae infection. In contrast, the serum levels of tumor necrosis factor alpha and interleukin-6 and spinal interleukin-6 levels were elevated, and the expression of major histocompatibility complex class II molecules, CD80, and CD86 on splenic dendritic cells were enhanced early after infection. Serum cytokine concentrations were not elevated, and EAE was not aggravated by S. pneumoniae infection in Toll-like receptor 2 (TLR2)-deficient mice. In conclusion, infection with S. pneumoniae worsens EAE probably by elevation of proinflammatory cytokines and activation of dendritic cells in the systemic circulation via TLR2 and cross talk through the blood-brain barrier.

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