Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance

Fu, Dongdong; Senouthai, Soulixay; Wang, Junjie; You, Yun

doi:10.1186/s12882-019-1548-y

Cited by 17 publications

(20 citation statements)

References 30 publications

(27 reference statements)

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“…This claim is supported by numerous experimental studies in both animal models and ex vivo samples of patients [5,[155][156][157][158]. VIP was able to decrease the cytokine profile and master regulators related to Th1 and Th17 subsets and to increase those of them related to Treg or Th2 in different autoimmunity animal models, such as the collagen-induced (CIA) arthritis mouse model of RA, the TNBS mouse model of Crohn's disease, the nonobese diabetic (NOD) mouse model of autoimmune diabetes, the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, the experimental model of autoimmune myocarditis, and the pristine-induced lupus model of lupus nephritis [7,11,[159][160][161][162][163][164][165]. In addition, this immunomodulatory role of VIP was observed in two inflammatory animal models, including the models of CNS inflammation or atherosclerosis [108,164].…”

Section: Regulating Th Cellsmentioning

confidence: 99%

“…VIP not only acts on a specific subset in these pathologies, but is also able to balance the different Th subsets, inducing nonpathogenic phenotypes or modify their plasticity. Studies on different transcription factors, cytokines, cytokine receptors, chemokines, and chemokine receptors in the above mentioned mice models, in vitro or ex vivo, showed that VIP counterbalances the ratio of Th1/Th2, Th17/Treg, Th1/Treg, or Th2/Th9, reducing pathogenicity and increasing tolerance [10,165,168]. Th17 cells are a heterogeneous subset with a nonpathogenic or pathogenic profile, depending on the microenvironment.…”

Section: Regulating Th Cellsmentioning

confidence: 99%

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A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.

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Section: Regulating Th Cellsmentioning

confidence: 99%

Section: Regulating Th Cellsmentioning

confidence: 99%

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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“…Approximately, 60% of patients with proliferative SLE progress to end-stage renal disease, and lupus nephritis (LN) is considered a major cause of mortality in SLE patients. 7 Although the pathogenesis of LN is unclear, defective immune regulatory mechanisms, such as impaired T helper (Th) cell function, including Th1/Th2 and Th17/regulatory T cell imbalance, have been recognized as important contributors to the aetiology of SLE. 8 Proinflammatory cytokines stimulate plasma cells to produce autoantibodies that promote organ damage.…”

Section: Introductionmentioning

confidence: 99%

Denervation‐induced loss of skeletal muscle mass influences immune homeostasis and accelerates the disease progression of lupus nephritis

Liu

Kiyoi

Takemasa

et al. 2020

JCSM Clinical Reports

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BackgroundPatients with systemic autoimmune disease are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. How sarcopenic status affects disease progression remains unknown. The present study explored the influence of denervation‐induced sarcopenia on immune homeostasis and investigated related biological pathways that might be important for future disease management.MethodsA denervation‐induced skeletal muscle loss model was established, and the function of the immune system was evaluated. Immune cell proportions and cytokine levels in peripheral blood and atrophied skeletal muscle were profiled. We examined store‐operated Ca2+ entry and mitochondrial function in immune cells. MRL/lpr mice were used to evaluate the influence of denervation‐induced sarcopenia on autoimmune progression in lupus nephritis.ResultsCompared with splenocyte fractions obtained from sham mice, proportions of CD4+ cells, CD8+ cells, CD19+CD20− cells, CD49b+NK46+ cells, CD4+IL‐4+ cells, and CD4+FoxP3+ cells were significantly decreased, whereas CD19+CD20+ cells, CD4+IFN‐γ+ cells, and CD4+IL17+ cells were markedly increased in sciatic nerve axotomy (SNA) mice. The serum cytokine profile indicated that SNA significantly increased the protein expressions of IL‐12p70 (P = 0.014), IL‐17A (P = 0.007), and IFN‐γ (P < 0.001). In SNA mice, there was an 18.74% decrease in peak Ca2+ influx (P < 0.001) and an 18.22% decrease in initial Ca2+ influx (P < 0.001) rates in peripheral T cells compared with sham mice. Mitochondrial respiration was significantly reduced in peripheral T cells from SNA mice compared with sham mice. SNA substantially promoted disease progression in lupus model mice demonstrated by the results of proteinuria monitoring, serum levels of blood urea nitrogen, and kidney histological scores.ConclusionsThe loss of skeletal muscle impaired mitochondrial respiration and activation in T cells and influenced the balance of T helper cell subsets. Therefore, denervation‐induced sarcopenia might promote the progression of autoimmune diseases, such as lupus nephritis, and enhance Th1/Th17 functions. These results suggest that physicians should be aware of the impact of the loss of skeletal muscle on the management of autoimmune disease and that a multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia.

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“…Regulatory T (Treg) cells, characterised by their cell surface markers: CD4, CD25, and Foxp3, are present in the peripheral blood and spleen and mediate remarkable immunosuppressive effects [4,5]. The importance of regulatory T cells in immunoregulation and tolerance development has been well demonstrated [6,13]. Speci cally, the expression of the transcription factor fork head box p3 (Foxp3) determined the development and differentiation of Treg cells [14], and its increase activated CD4 + CD25 + Treg cells in vitro [15].…”

Section: Introductionmentioning

confidence: 99%

“…Speci cally, the expression of the transcription factor fork head box p3 (Foxp3) determined the development and differentiation of Treg cells [14], and its increase activated CD4 + CD25 + Treg cells in vitro [15]. However, the dysregulation of Tregs is a pivotal factor for the development of LN [13], and a pool of Foxp3 + Treg cells has been associated with LN features.…”

Section: Introductionmentioning

confidence: 99%

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

Gong

Guo

et al. 2020

Preprint

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Background: Fractalkine is a chemokine with several roles, including chemotaxis, adhesion, and immune damage. It participates in cell inflammation and apoptosis and responds to the pathogenesis of autoimmune diseases. On the other hand, Treg cells are involved in autoimmune diseases. This study aimed to explore the regulatory mechanism of Fractalkine in renal injury and Treg apoptosis via the p38MAPK signalling pathway in lupus-prone mice. Methods: Lupus was induced in BALB/c female mice by injection of pristane. Then, CD4+ CD5+ Treg cells were isolated from the spleen of lupus mice. To deplete Fractalkine, first, mice received an injection of anti-Fractalkine antibody. Later, the transfection of Treg cells with Fractalkine siRNA was conducted. Lupus mice and Treg cells were treated with the p38MAPK inhibitor SB203580 and/or activator U-46619, respectively. The levels of urine protein, serum urea nitrogen, creatinine, and autoantibodies were measured from mouse samples, and renal histopathological features were analysed. The expression of Fractalkine, p-p38, Foxp3, IL-6, and IL-17 in the mouse kidney and Treg cells was detected. The levels of apoptosis and key apoptotic factors: Bax, Bcl-2, and Cyt-c in Treg cells were analysed. Results: The expression of Fractalkine, p-p38, IL-6, and IL-17 increased; meanwhile, that of Foxp3 decreased in the kidneys of mice with lupus. The depletion of Fractalkine and p38MAPK levels ameliorated proteinuria and renal functions and significantly reduced serum autoantibodies, renal Fractalkine, p-p38, IL-6, and IL-17 levels, while increasing renal Foxp3 concentration in lupus mice. The effects of Fractalkine knockdown (KD) and p38MAPK inhibitor on Treg cells, derived from lupus mice, were consistent with those observed in the kidneys. In addition, Fractalkine KD reduced cell apoptosis and suppressed the activation of p38MAPK signalling in Treg cells, derived from lupus mice. Meanwhile, the p38MAPK activator U-46619 had the opposite effect. Conclusion: Together, our data indicated that Fractalkine promoted the nephritis progression in lupus mice, most likely through the regulation of Treg cell apoptosis and activation of the p38MAPK signalling pathway. It suggested that targeting Fractalkine is a potential therapeutic strategy for treating LN.

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Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance

Cited by 17 publications

References 30 publications

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Denervation‐induced loss of skeletal muscle mass influences immune homeostasis and accelerates the disease progression of lupus nephritis

Depletion of Fractalkine Ameliorates Renal Injury and Treg Cell Apoptosis Via the p38MAPK Pathway in Lupus-prone Mice

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