The Role of Dendritic Cells in Tissue-Specific Autoimmunity

Mbongue, Jacques C.; Nicholas, Dequina; Firek, Anthony; Langridge, William H. R.

doi:10.1155/2014/857143

Cited by 75 publications

(51 citation statements)

References 159 publications

(180 reference statements)

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“…The key cells of the innate immune response are the dendritic cells and NK cells, and the principal cells involved in the adaptive immune response are the Th lymphocytes, gamma delta (cd) lymphocytes, and regulatory T cells (Tregs). NKT cells exhibit features of both the innate and adaptive immune responses [238][239][240]. Tregs have been the principal cell population under active investigation in autoimmune hepatitis, but NKT cells have been emerging as another population with important immune modulatory functions.…”

Section: Insights Into the Principal Cell Mediators Of Autoimmune Hepmentioning

confidence: 99%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.

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Section: Insights Into the Principal Cell Mediators Of Autoimmune Hepmentioning

confidence: 99%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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“…The increasing prevalence of IDDM, its progressive complications, and the lack of effective preventive and curative strategies require a greater effort to develop effective and safe methods for persistent restoration of normal blood sugar levels in IDDM patients. So far, no safe and effective treatment is available to control the onset and progression this life-long debilitating disease (3). The loss of β-cell function in IDDM is mediated principally by CD4 + and CD8 + T cells, and autoreactive effector CD8 + T cells (CTLs) were shown to be responsible for islet β-cell destruction in the non-obese diabetic (NOD) mouse and in human IDDM (4–6).…”

Section: Introductionmentioning

confidence: 99%

The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus

et al. 2017

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Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens. During activation, the iDCs become mature. Maturation begins when the DCs cease taking up antigens and begin to migrate from their location in peripheral tissues to adjacent lymph nodes or the spleen where during their continued maturation the DCs present stored antigens on surface MHCII receptor molecules to naive Th0 cells. During antigen presentation, the DCs upregulate the biosynthesis of costimulatory receptor molecules CD86, CD80, CD83, and CD40 on their plasma membrane. These activated DC receptor molecules bind cognate CD28 receptors presented on the Th0 cell membrane, which triggers DC secretion of IL-12 or IL-10 cytokines resulting in T cell differentiation into pro- or anti-inflammatory T cell subsets. Although basic concepts involved in the process of iDC activation and guidance of Th0 cell differentiation have been previously documented, they are poorly defined. In this review, we detail what is known about the process of DC maturation and its role in the induction of insulin-dependent diabetes mellitus autoimmunity.

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“…[23][24][25] In addition, CD86 and IL-12 are crucial for Th1 priming, whereas no exact mechanism for the regulation of Th2 exists. 26,27 Recent studies have indicated that DCs are associated with brotic diseases.…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

et al. 2018

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Silicosis is one of the most common occupational respiratory diseases caused by inhaling silica dust over a prolonged period of time, and the progression of silicosis is accompanied with chronic inflammation and progressive pulmonary fibrosis, in which dendritic cells (DCs), the most powerful antigen presentation cell (APC) in the immune response, play a crucial role. To investigate the role of DCs in the development of silicosis, we established an experimental silicosis rat model and examined the number of DCs and alveolar macrophages (AMs) in lung tissues using immunofluorescence over 84 days. Additionally, to obtain an overview of the immunological changes in rat lung tissues, a series of indicators including Th1/Th2 cells, IFN-g, IL-4, MHC-II, CD80/86 and IL-12 were detected using flow cytometry and an enzyme-linked immunosorbent assay (ELISA) as well as a real-time polymerase chain reaction (PCR) assay. We observed that the number of DCs slightly increased at the inflammatory stage, and it increased significantly at the final stage of fibrosis. Polarization of Th1 cells and IFN-g expressions were dominant during the inflammatory stage, whereas polarization of Th2 cells and IL-4 expressions were dominant during the fibrotic stage. The subsequent mechanistic study found that the expressions of MHC-II, CD80/86 and IL-12, which are the key molecules that connect DCs and Th cells, changed dynamically in the experimental silicosis rat model. The data obtained in this study indicated that the increase in DCs may contribute to polarization of Th1/Th2 cells via MHC-II, CD80/86, and IL-12 in silica dust-exposed rats.

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The Role of Dendritic Cells in Tissue-Specific Autoimmunity

Cited by 75 publications

References 159 publications

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

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