The Environment of Regulatory T Cell Biology: Cytokines, Metabolites, and the Microbiome

Hoeppli, R.; Wu, Dan; Cook, Laura; Levings, Megan K.

doi:10.3389/fimmu.2015.00061

Cited by 125 publications

(98 citation statements)

References 231 publications

(212 reference statements)

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“…Similar results were also observed in other studies, where there is a decrease of suppressive ability of Tregs in SLE patients in modulating other Th cell subsets (13,17). The composition of the local milieu, including the types of cytokines, can influence Treg function (18). Some pro-inflammatory cytokines, such as IFN type I (IFN-α) and IL-6 have been found to affect Treg function in SLE patients (19,20).…”

Section: Development Of Th Cell Subset Percentages After Pristane Injsupporting

confidence: 73%

Regulatory T Cells Compensation Failure Cause the Dysregulation of Immune Response in Pristane Induced Lupus Mice Model

Kalim

Pratama

Nugraha

et al. 2018

MJMS

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Introduction: Regulatory T cells' (Tregs') role remains unclear in the pathogenesis of systemic lupus erythematosus (SLE). This study was aimed at monitoring the percentage of Tregs within 32 weeks and monitoring its relationship with the percentage of other T helper (Th) cell subsets and the levels of autoantibodies and pro-inflammatory cytokines in a murine SLE model induced by pristane.Methods: Forty-eight female BALB/c mice were divided into a healthy control (HC) and a pristine-induced (PI) group. SLE was induced by a single 0.5 cc pristane intraperitoneal injection. Six from each group were sacrificed every eight weeks until 32 weeks post-pristane injection. Treg, Th1, Th2 and Th17 percentages from the spleen were measured using flowcytometry. ANA, IL-6 and IFN-α levels were measured from serum using ELISA.Results: The Treg percentage from the PI group increased significantly at 16 weeks compared to the HC group, while Th1, Th2 and Th17 percentages decreased. Tregs in the PI group began to reduce from the 24th to 32nd weeks, followed by an elevation of the Th1, Th2 and Th17 percentages. Tregs were negatively correlated with Th1 and Th2. Tregs in the PI group had a negative correlation with ANA and IFN-α levels from serum, whereas Tregs had a positive correlation with IL-6 levels.Conclusion: The compensation of Tregs observed at 16 weeks after pristane injection failed, marked by a decreasing number of Tregs, followed by an increase of Th subsets, proinflammatory cytokines and autoantibodies. This compensatory failure of Tregs could be affected by pro-inflammatory cytokines, such as IFN-α and IL-6.

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Section: Development Of Th Cell Subset Percentages After Pristane Injsupporting

confidence: 73%

Regulatory T Cells Compensation Failure Cause the Dysregulation of Immune Response in Pristane Induced Lupus Mice Model

Kalim

Pratama

Nugraha

et al. 2018

MJMS

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“…Recent studies, utilizing metabolome analysis and other investigative techniques, have revealed that the number of colonic Tregs in steady-state conditions are heavily influenced or even determined by the luminal concentration of propionate, butyrate, and perhaps acetate, produced by commensal bacteria [105][106][107]. The precise mechanisms by which SCFAs promote the production of colonic Tregs are still a matter of debate and may well vary with the SCFAs involved.…”

Section: Effects On Regulatory T Cell Productionmentioning

confidence: 97%

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

Morris¹,

et al. 2016

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There is a growing awareness that gut commensal metabolites play a major role in host physiology and indeed the pathophysiology of several illnesses. The composition of the microbiota largely determines the levels of tryptophan in the systemic circulation and hence, indirectly, the levels of serotonin in the brain. Some microbiota synthesize neurotransmitters directly, e.g., gamma-amino butyric acid, while modulating the synthesis of neurotransmitters, such as dopamine and norepinephrine, and brain-derived neurotropic factor (BDNF). The composition of the microbiota determines the levels and nature of tryptophan catabolites (TRYCATs) which in turn has profound effects on aryl hydrocarbon receptors, thereby influencing epithelial barrier integrity and the presence of an inflammatory or tolerogenic environment in the intestine and beyond. The composition of the microbiota also determines the levels and ratios of short chain fatty acids (SCFAs) such as butyrate and propionate. Butyrate is a key energy source for colonocytes. Dysbiosis leading to reduced levels of SCFAs, notably butyrate, therefore may have adverse effects on epithelial barrier integrity, energy homeostasis, and the T helper 17/regulatory/T cell balance. Moreover, dysbiosis leading to reduced butyrate levels may increase bacterial translocation into the systemic circulation. As examples, we describe the role of microbial metabolites in the pathophysiology of diabetes type 2 and autism.

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“…Moreover, recent studies highlighted the immunosuppressive potential of other cell types including uterine natural killer (uNK) cells and mesenchymal stem cells (MSCs) [8,9]. One of the hallmarks of regulatory cell populations is their remarkable plasticity as they can be positively or negatively modulated by a broad spectrum of cytokines, chemokines, growth factors and costimulatory signals that tailor their differentiation, expansion, stability and survival [10]. Moreover, although underappreciated for many years, emerging observations suggest essential roles for endogenous glycan-binding proteins or lectins and their corresponding glycosylated ligands in controlling the fate and function of immune regulatory cells [11].…”

Section: Immune Cell Homeostatic Programs Regulated By Galectin-glycamentioning

confidence: 99%

Re‐wiring regulatory cell networks in immunity by galectin–glycan interactions

et al. 2015

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Edited by Wilhelm JustKeywords: Galectin Regulatory T cell Tolerogenic dendritic cell M2-type macrophage Myeloid-derived suppressor cell Immunosuppression a b s t r a c tPrograms that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloidderived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.

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The Environment of Regulatory T Cell Biology: Cytokines, Metabolites, and the Microbiome

Cited by 125 publications

References 231 publications

Regulatory T Cells Compensation Failure Cause the Dysregulation of Immune Response in Pristane Induced Lupus Mice Model

Regulatory T Cells Compensation Failure Cause the Dysregulation of Immune Response in Pristane Induced Lupus Mice Model

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

Re‐wiring regulatory cell networks in immunity by galectin–glycan interactions

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