Regulatory T-Cells: Diverse Phenotypes Integral to Immune Homeostasis and Suppression

GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Toxicologic Pathology (Impact Factor: 2.14). 01/2012; 40(2):186-204. DOI: 10.1177/0192623311430693
Source: PubMed


Regulatory T-cells (T(REG)) are diverse populations of lymphocytes that regulate the adaptive immune response in higher vertebrates. T(REG) delete autoreactive T-cells, induce tolerance, and dampen inflammation. T(REG) cell deficiency in humans (i.e., IPEX [Immunodysregulation, Polyendocrinopathy and Enteropathy, X-linked syndrome]) and animal models (e.g., "Scurfy" mouse) is associated with multisystemic autoimmune disease. T(REG) in humans and laboratory animal species are similar in type and regulatory function. A molecular marker of and the cell lineage specification factor for T(REG) is FOXP3, a forkhead box transcription factor. CD4(+) T(REG) are either natural (nT(REG)), which are thymus-derived CD4(+)CD25(+)FOXP3(+) T-cells, or inducible (i.e., Tr1 cells that secrete IL-10, Th3 cells that secrete TGF-β and IL-10, and Foxp3(+) Treg). The proinflammatory Th17 subset has been a major focus of research. T(H)17 CD4(+) effector T-cells secrete IL-17, IL-21, and IL-22 in autoimmune and inflammatory disease, and are dynamically balanced with T(REG) cell development. Other lymphocyte subsets with regulatory function include: inducible CD8(+) T(REG), CD3(+)CD4(-)CD8(-) T(REG) (double-negative), CD4(+)Vα14(+) (NKT(REG)), and γδ T-cells. T(REG) have four regulatory modes of action: secretion of inhibitory cytokines (e.g., IL-10 and TGF-β), granzyme-perforin-induced apoptosis of effector lymphocytes, depriving effector T-cells of cytokines leading to apoptosis, or inhibition of dendritic cell function. The role of T(REG) in mucosal sites, inflammation/infection, pregnancy, and cancer as well as a review of T(REG) as a modulatory target in drug development will be covered.

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Available from: Richard A Peterson, Oct 20, 2014
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    • "Even T-reg response to quercetin could be a fine marker to probe the inflammatory injury due to heat stress, particularly because regulatory T cells need more time than the chemical activity on intracellular enzymatic and signaling systems needs. Furthermore, they modulate immune downregulation; therefore, T cells are proving to be reliable hallmarks of a balanced response to stressors [8]. The authors limited their testing to immune markers such as inflammatory cytokines, but it would be very interesting to also assay T-reg– derived cytokines in plasma samples. "
    Nutrition Research 02/2015; 35(4). DOI:10.1016/j.nutres.2015.01.006 · 2.47 Impact Factor
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    • "In addition to altering TLR-mediated inflammation and potentially DNA epigenetics, a mechanism by which alteration in microflora may drive immune-mediated disease involves the gut bacteria’s effect on regulatory T-cells (Tregs), the cell tasked with keeping the immune system in balance during both inflammation and homeostasis [117]. Alterations in the microbiome have been shown in both mice and (to a less extensive degree) humans to affect Treg development [118-122], and reduction in Treg signal is associated with worse outcomes in infection control [123], autoimmunity [124,125], allergic sensitization [126], and has been, more controversially, associated with cancer risks [127-129]. "
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    ABSTRACT: While numerous changes in human lifestyle constitute modern life, our diet has been gaining attention as a potential contributor to the increase in immune-mediated diseases. The Western diet is characterized by an over consumption and reduced variety of refined sugars, salt, and saturated fat. Herein our objective is to detail the mechanisms for the Western diet's impact on immune function. The manuscript reviews the impacts and mechanisms of harm for our over-indulgence in sugar, salt, and fat, as well as the data outlining the impacts of artificial sweeteners, gluten, and genetically modified foods; attention is given to revealing where the literature on the immune impacts of macronutrients is limited to either animal or in vitro models versus where human trials exist. Detailed attention is given to the dietary impact on the gut microbiome and the mechanisms by which our poor dietary choices are encoded into our gut, our genes, and are passed to our offspring. While today's modern diet may provide beneficial protection from micro- and macronutrient deficiencies, our over abundance of calories and the macronutrients that compose our diet may all lead to increased inflammation, reduced control of infection, increased rates of cancer, and increased risk for allergic and auto-inflammatory disease.
    Nutrition Journal 06/2014; 13(1):61. DOI:10.1186/1475-2891-13-61 · 2.60 Impact Factor
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    • "iTregs has considerable significance in preventing asthma if generated early enough in life [4]. In addition, Th3 cells that secrete TGF-β and IL-10 belong to this subset [17]. "
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    ABSTRACT: In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. The aim of the present study is to attempt to classify subtypes of Tregs and summarize their roles in allergy. Tregs should include natural Tregs (nTreg) including inducible costimulator (ICOS)(+) Tregs, inducible/adaptive Tregs (iTreg), interleukin (IL)-10-producing type 1 Tregs (Tr1 cells), CD8(+) Tregs and IL-17-producing Tregs. These cells share some common features including expression of Foxp3 (except for Tr1 cells), and secretion of inhibitory cytokine IL-10 and/or TGF-beta. Furthermore, it is noticeable that Tregs likely contribute to allergic disorders such as dermatitis and airway inflammation, and play a crucial role in the treatment of allergy through their actions on suppression of effector T cells and inhibition of activation of mast cells and basophils. Modulation of functions of Tregs may provide a novel strategy to prevent and treat allergic diseases.
    Journal of Translational Medicine 05/2014; 12(1):125. DOI:10.1186/1479-5876-12-125 · 3.93 Impact Factor
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