The Balancing Act of Autoimmunity: Central and Peripheral Tolerance Versus Infection Control

Thomas, Ranjeny

doi:10.3109/08830180903434219

Cited by 6 publications

(5 citation statements)

References 124 publications

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“…Too much immunity results in autoimmune disorders, and too little immunity results in infections. Thus, optimal immunity requires a balance between autoimmunity and opportunistic infections (Thomas, 2010; Fujio et al, 2012). There are no exact cutoff values that define high, optimal, or low immunity levels for inflammatory mediators.…”

Section: General Overview Of the Biology Of Diabetic Nephropathymentioning

confidence: 99%

Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis

Kanasaki¹,

Taduri²,

Koya³

2013

Front. Endocrin.

191

144

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Kidney disease associated with diabetes mellitus is a major health problem worldwide. Although established therapeutic strategies, such as appropriate blood glucose control, blood pressure control with renin–angiotensin system blockade, and lipid lowering with statins, are used to treat diabetes, the contribution of diabetic end-stage kidney disease to the total number of cases requiring hemodialysis has increased tremendously in the past two decades. Once renal function starts declining, it can result in a higher frequency of renal and extra-renal events, including cardiovascular events. Therefore, slowing renal function decline is one of the main areas of focus in diabetic nephropathy research, and novel strategies are urgently needed to prevent diabetic kidney disease progression. Regardless of the type of injury and etiology, kidney fibrosis is the commonly the final outcome of progressive kidney diseases, and it results in significant destruction of normal kidney structure and accompanying functional deterioration. Kidney fibrosis is caused by prolonged injury and dysregulation of the normal wound-healing process in association with excess extracellular matrix deposition. Kidney fibroblasts play an important role in the fibrotic process, but the origin of the fibroblasts remains elusive. In addition to the activation of residential fibroblasts, other important sources of fibroblasts have been proposed, such as pericytes, fibrocytes, and fibroblasts originating from epithelial-to-mesenchymal and endothelial-to-mesenchymal transition. Inflammatory cells and cytokines play a vital role In the process of fibroblast activation. In this review, we will analyze the contribution of inflammation to the process of tissue fibrosis, the type of fibroblast activation and the therapeutic strategies targeting the inflammatory pathways in an effort to slow the progression of diabetic kidney disease.

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Section: General Overview Of the Biology Of Diabetic Nephropathymentioning

confidence: 99%

Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis

Kanasaki¹,

Taduri²,

Koya³

2013

Front. Endocrin.

191

144

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“…Firstly, by a reduction in suppressor T cell (T regulatory cell) activity; secondly, due to the modification of normal self-antigens, by drugs, environmental chemicals, viruses, or mutations; and thirdly, due to an exposure in the direction of an antigen that is very similar to self-antigen ("molecular mimicry"). This is a good example of how important it is for the immune system to stay in balance with itself since any imbalance may cause a threat and might bring about unwanted repercussions [35][36][37][38].…”

Section: Autoimmunitymentioning

confidence: 99%

Agaricus blazei Murill - immunomodulatory properties and health benefits

Biedroń

Tangen

Maresz

et al. 2012

FFHD

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The Agaricus blazei Murill (AbM), also known as Agaricus brasiliensis L. due to its origin in Brazilian rain forest, is an edible mushroom of the Basidiomycetes family, which also comprises medicinal mushrooms such as Hericium erinaceus and Grifola frondosa. AbM has been used in traditional medicine locally and also recently as a health food worldwide. Since it has been found to possess immunomodulatory properties, its biological and health-related effects, as well as its isolated active ingredients e.g. beta-glucans, have been examined by scientists. Other investigations have been performed with mixed mushroom products, such as AndoSan TM , which contains mostly AbM, but also the two other mushrooms above. AbM-related benefits reviewed here include effects against cancer, infections, inflammation, allergy/ asthma and diabetes. Effects of AndoSan TM and other AbM-based extracts have been compared in a bacterial sepsis model.

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“…Moreover, mice in which DCs and Langerhans cells are extensively ablated develop severe autoimmune disease associated with myeloid proliferation and T and B lymphocyte activation, demonstrating the essential constitutive role that DCs play in peripheral self-tolerance (1). The mechanisms by which DCs maintain peripheral tolerance are still unclear, but they include central or peripheral clonal deletion, ignorance, anergy, and regulation, both through induction of functional regulatory T cells (Tregs) and through immunosuppressive mechanisms (2). The elucidation of tolerance mechanisms has important implications for development of Ag-specific immunotherapeutic strategies for autoimmune and allergic disease and allografting.…”

Section: Endritic Cells (Dcs) Comprise a Heterogeneous Group Ofmentioning

confidence: 99%

Immunotherapy with Costimulatory Dendritic Cells To Control Autoimmune Inflammation

O’Sullivan

Pai

Street

et al. 2011

The Journal of Immunology

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Costimulation-deficient dendritic cells (DCs) prevent autoimmune disease in mouse models. However, autoimmune-prone mice and humans fail to control expansion of peripheral autoreactive effector memory T cells (TEMs), which resist immunoregulation by costimulation-deficient DCs. In contrast, activation of DC costimulation may be coupled with regulatory capacity. To test whether costimulatory DCs control TEMs and attenuate established autoimmune disease, we used RelB-deficient mice, which have multiorgan inflammation, expanded peripheral autoreactive TEMs, and dysfunctional Foxp3+ regulatory T cells (Tregs) cells and conventional DCs. TEMs were regulated by Foxp3+ Tregs when costimulated by CD3/CD28-coated beads or wild-type DCs but not DCs deficient in RelB or CD80/CD86. After transfer, RelB and CD80/CD86-sufficient DCs restored tolerance and achieved a long-term cure of autoimmune disease through costimulation of TEM and Foxp3+ Treg IFN-γ production, as well as induction of IDO by host APCs. IDO was required for regulation of TEMs and suppression of organ inflammation. Our data challenge the paradigm that costimulation-deficient DCs are required to regulate established autoimmune disease to avoid TEM activation and demonstrate cooperative cross-talk between costimulatory DCs, IFN-γ, and IDO-dependent immune regulation. IFN-γ and IDO activity may be good surrogate biomarkers measured against clinical efficacy in trials of autoimmune disease immunoregulation.

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The Balancing Act of Autoimmunity: Central and Peripheral Tolerance Versus Infection Control

Cited by 6 publications

References 124 publications

Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis

Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis

Agaricus blazei Murill - immunomodulatory properties and health benefits

Immunotherapy with Costimulatory Dendritic Cells To Control Autoimmune Inflammation

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