Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies?

2013 ◽  
Vol 19 (8) ◽  
pp. 995-1002 ◽  
Author(s):  
AH Nuyts ◽  
WP Lee ◽  
R Bashir-Dar ◽  
ZN Berneman ◽  
N Cools
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Dc Function ◽  
Key Players ◽  
Plasmacytoid Dcs ◽  
And Function

Many studies have demonstrated the role of the adaptive immune system in the pathogenesis of multiple sclerosis (MS). Recent data suggest that dendritic cells (DCs), which are innate immune cells, also contribute to the pathogenesis of MS. In patients with MS, DCs are abundantly present in brain lesions, and display an altered phenotype and/or function as compared with this in healthy controls. DCs are thus in the position to pathologically influence the effector function of (auto-reactive) T and B cells. Interestingly, current first-line immunomodulating therapies for MS have been shown to restore DC phenotype and function, albeit in a non-specific manner. To date, clinical trials using agents specifically targeting DC function are ongoing. Moreover, several studies worldwide are currently investigating possible strategies to develop tolerogenic DCs. This review focuses on the phenotypic and functional alterations of conventional DCs and plasmacytoid DCs in patients with MS. Furthermore, we discuss how existing immunomodulating therapies for MS patients affect DC function and address future perspectives in the development of immunotherapies specifically targeting DCs.

scholarly journals The Role of Lipopeptidophosphoglycan in the Immune Response toEntamoeba histolytica

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Isabel Wong-Baeza ◽  
Marcela Alcántara-Hernández ◽  
Ismael Mancilla-Herrera ◽  
Itzmel Ramírez-Saldívar ◽  
Lourdes Arriaga-Pizano ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Amebic Liver Abscess ◽  
Disease Development ◽  
Dependent Manner ◽  
Surface Molecule ◽  
Adaptive Immune ◽  
Molecular Patterns

The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune receptors, such as Toll-like receptors (TLRs), is the first step in the inflammatory response to pathogens.Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a “Pamptigen”), it may be a good candidate to develop a vaccine againstE. histolyticainfection and an effective adjuvant.

scholarly journals CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Kim Ohl ◽  
Anastasia Schippers ◽  
Klaus Tenbrock
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
B Cells ◽  
Germinal Center ◽  
Adaptive Immune System ◽  
Transcriptional Regulator ◽  
Adaptive Immune ◽  
Dc Function ◽  
Specific Deletion

Dendritic cells (DCs) are crucial for the balance between immune response and tolerance, but the molecular mechanism regulating development, differentiation, and homeostasis are poorly understood. The transcriptional activator CREB is involved in regulating different cells of the innate and adaptive immune system and is a transcriptional regulator of development, survival, activation, or proliferation in macrophages, dendritic cells, B cells, and T cells. To directly examine the role of CREB in the regulation of DCs, the CREB gene was targeted for deletion with a CD11c-cre transgene. The deletion of CREB in CD11c+ cells did not involve any developmental or systemic defects within DC populations. However, CREB deficiency in CD11c+ cells reduced germinal center (GC) B cells in steady state, and immunization with NP-CGG resulted in a reduced formation of GCs, paralleled by the reduced production of IgGs in sera of immunized mice. In conclusion, we demonstrate that CREB expression in CD11c+ cells enhances germinal center responses, most likely by altering DC function, which might have implications for autoimmune diseases that are associated with dysregulated GC responses.

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

scholarly journals Impact of Andropause on Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria C. Ysrraelit ◽  
Jorge Correale
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Adaptive Immune Response ◽  
Epidemiological Studies ◽  
Testosterone Levels ◽  
Adaptive Immune ◽  
Natural Decrease ◽  
And Function ◽  
Gonadal Failure

Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.

scholarly journals Genetic Diversity of Toll-Like Receptors and Immunity toM. lepraeInfection

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Bryan E. Hart ◽  
Richard I. Tapping
Keyword(s):  
Association Studies ◽  
Genetic Association Studies ◽  
Adaptive Immune System ◽  
Mycobacterial Infection ◽  
Innate Immune ◽  
Genetic Associations ◽  
Toll Like Receptors ◽  
Adaptive Immune ◽  
Polymorphic Variants ◽  
And Function

Genetic association studies of leprosy cohorts across the world have identified numerous polymorphisms which alter susceptibility and outcome to infection withMycobacterium leprae. As expected, many of the polymorphisms reside within genes that encode components of the innate and adaptive immune system. Despite the preponderance of these studies, our understanding of the mechanisms that underlie these genetic associations remains sparse. Toll-like receptors (TLRs) have emerged as an essential family of innate immune pattern recognition receptors which play a pivotal role in host defense against microbes, including pathogenic strains of mycobacteria. This paper will highlight studies which have uncovered the association of specific TLR gene polymorphisms with leprosy or tuberculosis: two important diseases resulting from mycobacterial infection. This analysis will focus on the potential influence these polymorphic variants have on TLR expression and function and how altered TLR recognition or signaling may contribute to successful antimycobacterial immunity.

scholarly journals Innate Pathways of Immune Activation in Transplantation

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Todd V. Brennan ◽  
Keri E. Lunsford ◽  
Paul C. Kuo
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Immune Recognition ◽  
First Line ◽  
Adaptive Immune

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity.

scholarly journals Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

2017 ◽  
Vol 214 (6) ◽  
pp. 1769-1785 ◽  
Author(s):  
Silvia Cerboni ◽  
Nadia Jeremiah ◽  
Matteo Gentili ◽  
Ulf Gehrmann ◽  
Cécile Conrad ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Inflammatory Gene Expression ◽  
Adaptive Immune ◽  
Cyclic Dinucleotide

Activation of the cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is critical for IFN and inflammatory gene expression during innate immune responses. However, the role of STING in adaptive immunity is still unknown. In this study, we show that STING activation reduces the proliferation of T lymphocytes. This activity was independent of TBK1 and IRF3 recruitment and of type I IFN but required a distinct C-terminal domain of STING that activates NF-κB. Inhibition of cell proliferation by STING required its relocalization to the Golgi apparatus and caused mitotic errors. T lymphocytes from patients carrying constitutive active mutations in TMEM173 encoding STING showed impaired proliferation and reduced numbers of memory cells. Endogenous STING inhibited proliferation of mouse T lymphocytes. Therefore, STING, a critical innate sensor, also functions intrinsically in cells of the adaptive immune system to inhibit proliferation.

scholarly journals The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1280 ◽  
Author(s):  
Alessandro Maglione ◽  
Simona Rolla ◽  
Stefania Federica De Mercanti ◽  
Santina Cutrupi ◽  
Marinella Clerico
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Cell Types ◽  
Point Of View ◽  
Adaptive Immune ◽  
Future Path

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS.

Dendritic Cells as Arbiters of Peritoneal Immune Responses

2006 ◽  
Vol 26 (1) ◽  
pp. 8-25 ◽  
Author(s):  
Michelle L. McCully ◽  
Joaquín Madrenas
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Dendritic Cell Differentiation ◽  
Adaptive Immune ◽  
The Past ◽  
Key Players ◽  
And Function

During the past few years, there has been a substantial increase in the understanding of innate immunity. Dendritic cells are emerging as key players in the orchestration of this early phase of immune responses, with a role that will translate into the subsequent type of adaptive immune response against infection. Here we provide an overview of dendritic cell differentiation and function, with particular emphasis on those features unique to the immune defense of the peritoneal cavity and in the context of peritoneal dialysis-associated immune responses. The reader is referred to the primary references included in the accompanying list for specific details in this fascinating field.

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