Sodium chloride triggers Th17 mediated autoimmunity

Haase, Stefanie; Wilck, Nicola; Kleinewietfeld, Markus; Müller, Dominik N.; Linker, Ralf A.

doi:10.1016/j.jneuroim.2018.06.016

Cited by 30 publications

(24 citation statements)

References 61 publications

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“…The majority of these macrophages/microglia exhibited an inflammatory phenotype. Although unaddressed in the current study, it has been reported that high salt levels also imbalance adaptive immunity by inducing pathologic Th17 cells [27] and promoting a proinflammatory Treg phenotype with heightened IFNγ secretion and a diminished suppressive capacity [28]. While a balanced immune response requires precise regulation, the data from this study and from previous literature indicated that salt may tilt the balance toward a proinflammatory phenotype.…”

Section: Discussioncontrasting

confidence: 46%

High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism

Fan

Oladiran

Shi

et al. 2020

J Neuroinflammation

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Background: Though it is well-known that a high-salt diet (HSD) is associated with many chronic diseases, the effects of long-term high-salt intake on physiological functions and homeostasis remain elusive. In this study, we investigated whether and how an HSD affects mouse nociceptive thresholds, and myeloid cell trafficking and activation. Methods: Healthy C57BL/6 male and female mice were fed an HSD (containing 4% NaCl in chow and 1% NaCl in water) from the time of weaning for 3 to 4 months. Circulating monocytes, nerve macrophages, spinal microglia, and associated inflammatory responses were scrutinized using flow cytometry, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR) approaches. Mouse pain sensitivity to mechanical stimuli was monitored with von Frey tests along the experimental duration. Results: Mice on an HSD have reduced mechanical thresholds. They feel more pain than those on a normal diet (ND), e.g., regular laboratory chow (0.3% NaCl in chow). An HSD induced not only a remarkable expansion of circulating monocytes, CCR2 + Ly6C hi inflammatory monocytes in particular, but also an accumulation of CD11b + F4/ 80 + macrophages in the peripheral nerves and an activation of Iba-1 + spinal microglia. Replacing an HSD with a ND was unable to reverse the HSD-induced mechanical hypersensitivity or rescue the altered immune responses. However, treating HSD-fed mice with a chemokine receptor CCR2 antagonist effectively normalized the pain thresholds and immune cell profile in the periphery and spinal cord. An HSD failed to alter pain thresholds and myeloid cell activation in CCR2-deficient mice. Spinal microglial activation is required for HSD-induced mechanical hypersensitivity in male, but not in female mice. Conclusion: Overall, this study provides evidence that an HSD has a long-term impact on physiological function. CCR2-mediated cellular response, including myeloid cell trafficking and associated inflammation, plays pivotal roles in salt-dietary modulation of pain sensitivity.

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Section: Discussioncontrasting

confidence: 46%

High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism

Fan

Oladiran

Shi

et al. 2020

J Neuroinflammation

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“…Besides implications in cardiovascular pathologies, recent data have clearly shown that high salt intake could profoundly modulate the immune system through direct and indirect mechanisms-mainly leading to shifts toward a pro-inflammatory milieu (6, 7). However, the majority of current in vivo data is based on studies in rodents, using protocols of extremes of high salt intake that likely cannot extrapolate to humans and therefore findings have to be analyzed carefully if they can apply to the human situation (7, 44). Nevertheless, few available studies in humans indicate that even moderate changes in salt intake could impact host immunity and clinical parameters in a similar manner compared to experimental animal studies.…”

Section: Discussionmentioning

confidence: 99%

High Salt Inhibits Tumor Growth by Enhancing Anti-tumor Immunity

et al. 2019

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Excess salt intake could affect the immune system by shifting the immune cell balance toward a pro-inflammatory state. Since this shift of the immune balance is thought to be beneficial in anti-cancer immunity, we tested the impact of high salt diets on tumor growth in mice. Here we show that high salt significantly inhibited tumor growth in two independent murine tumor transplantation models. Although high salt fed tumor-bearing mice showed alterations in T cell populations, the effect seemed to be largely independent of adaptive immune cells. In contrast, depletion of myeloid-derived suppressor cells (MDSCs) significantly reverted the inhibitory effect on tumor growth. In line with this, high salt conditions almost completely blocked murine MDSC function in vitro . Importantly, similar effects were observed in human MDSCs isolated from cancer patients. Thus, high salt conditions seem to inhibit tumor growth by enabling more pronounced anti-tumor immunity through the functional modulation of MDSCs. Our findings might have critical relevance for cancer immunotherapy.

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“…3,4 The pathways involved in the induction of T H 17 cells after high-salt intake are related to activation of the p38/mitogen-activated protein kinase, nuclear factor of activated T cells and serum glucocorticoid-regulated kinase pathways (Table 1). [3][4][5][6][7] Notably, recent investigations showed that high-salt intake is involved in the induction of inflammatory reactions through disturbance of the gut microbiota (see recent reviews 2,8 ). In this regard, Wilck et al found that a high-salt diet disturbs the murine gut microbiome and induces neuroinflammation through T H 17 expansion in the EAE-affected murine model.…”

Section: New Findings On the Role Of High-salt Intake In Induction Ofmentioning

confidence: 99%

“…1 In animal models of MS (e.g. [3][4][5][6][7] Notably, recent investigations showed that high-salt intake is involved in the induction of inflammatory reactions through disturbance of the gut microbiota (see recent reviews 2,8 ). 1 In addition to these important findings, new investigations have shown the role of high-salt intake in the pathogenesis of MS through induction of severe neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

“…

Multiple etiological factors are involved in the pathogenesis of multiple sclerosis (MS). [3][4][5][6][7] Notably, recent investigations showed that high-salt intake is involved in the induction of inflammatory reactions through disturbance of the gut microbiota (see recent reviews 2,8 ). However, new findings showed that a high-salt diet is involved in the induction of severe neuroinflammation through the aggravation of T helper 17 pathways and their inflammatory cytokines.

…”

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confidence: 99%

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Role of diet and gut microbiota in multiple sclerosis: New findings on the role of high‐salt intake in induction of neuroinflammation

Abdoli

Jahromi

Roustazadeh

2019

Clinical & Exp Neuroim

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Multiple etiological factors are involved in the pathogenesis of multiple sclerosis (MS). The recent study by Okuno et al. provides an insight into the interaction of gut microbiota and immune cells in MS. However, new findings showed that a high-salt diet is involved in the induction of severe neuroinflammation through the aggravation of T helper 17 pathways and their inflammatory cytokines. The synergistic effects of high-salt and high-fat intake in the induction of inflammatory reactions are also plausible. This article is a snapshot of the recent findings about the putative role of highsalt intake in the pathogenesis of MS.New findings on the role of high-salt intake in induction of neuroinflammation New findings revealed the interaction of gut microbiota and immune cells in MS. This topic was adeptly reviewed by Okuno et al. in a recent special issue of Clinical and Experimental Neuroimmunology. 1 As reviewed, the gut microbiota of MS patients has a distinct pattern in comparison with healthy individuals. 1 In animal models of MS (e.g. experimental autoimmune encephalomyelitis [EAE]), involvement of gut flora in augmentation of immune responses toward neural inflammation and autoantibody production has been observed as well. 1 In addition to these important findings, new investigations have shown the role of high-salt intake in the pathogenesis of MS through induction of severe neuroinflammation. 2 The first findings in this regard were published in two studies in 2013 in Nature, and showed that excessive salt intake augments the T helper 17 (T H 17) cells in the EAE mouse model. 3,4 The pathways involved in the induction of T H 17 cells after high-salt intake are related to activation of the p38/mitogen-activated protein kinase, nuclear factor of activated T cells and serum glucocorticoid-regulated kinase pathways (Table 1). [3][4][5][6][7] Notably, recent investigations showed that high-salt intake is involved in the induction of inflammatory reactions through disturbance of the gut microbiota (see recent reviews 2,8 ). In this regard, Wilck et al. found that a high-salt diet disturbs the murine gut microbiome and induces neuroinflammation through T H 17 expansion in the EAE-affected murine model. 9 Remarkably, neuroinflammation after high-salt exposure was related to disturbance of the mouse gut microbiome, especially depletion of Lactobacillus murinus. Conversely, recovery of L. murinus prohibited salt-induced neuropathology in the EAE model. 9 As such, in a pilot study in humans, high-salt intake diminished intestinal survival of Lactobacillus spp., and enhanced T H 17 cells and blood pressure. 9 Faraco et al. showed that high dietary salt induces neurovascular and cognitive dysfunction through a gut-initiated T H 17 responses. 10 Augmentation of these cells in the small intestine after a high-salt diet resulted in increased interleukin (IL)-17 concentration in the blood. These findings suggest a new gut-brain axis linking dietary salt intake. Although there is strong evidence regarding the pathogenesis...

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Sodium chloride triggers Th17 mediated autoimmunity

Cited by 30 publications

References 61 publications

High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism

High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism

High Salt Inhibits Tumor Growth by Enhancing Anti-tumor Immunity

Role of diet and gut microbiota in multiple sclerosis: New findings on the role of high‐salt intake in induction of neuroinflammation

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