BMSC-EVs regulate Th17 cell differentiation in UC via H3K27me3

Chen, Qianyun; Duan, Xueyun; Xu, Meng; Fan, Huiying; Dong, Yalan; Wu, Hui; Zhang, Man; Liu, Yujin; Zhang, Nan; Deng, Shuangjiao; Liu, Xingxing

doi:10.1016/j.molimm.2019.12.019

Cited by 28 publications

(17 citation statements)

References 37 publications

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“…Moreover, another study revealed that bone marrow MSC-EVs could inhibit the differentiation of Th17 cells in ulcerative colitis by regulating histone H3 lysine-27 trimethylation (H3K27me3) that is closely associated with the differentiation of Th17 cells. Therefore, MSC-EVs, which regulate H3K27me3, could be promising agents for inflammatory immune diseases associated with abnormal Th17 cell differentiation ( 283 ). Administration of MSC-EVs also increases the percentages of CD4 + CD25 + Foxp3 + Tregs in lymph nodes and the spleen ( 281 ).…”

Section: Immuno-properties Of Msc-evs and Mofmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

et al. 2021

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Severe trauma is the principal cause of death among young people worldwide. Hemorrhagic shock is the leading cause of death after severe trauma. Traumatic hemorrhagic shock (THS) is a complex phenomenon associating an absolute hypovolemia secondary to a sudden and significant extravascular blood loss, tissue injury, and, eventually, hypoxemia. These phenomena are responsible of secondary injuries such as coagulopathy, endotheliopathy, microcirculation failure, inflammation, and immune activation. Collectively, these dysfunctions lead to secondary organ failures and multi-organ failure (MOF). The development of MOF after severe trauma is one of the leading causes of morbidity and mortality, where immunological dysfunction plays a central role. Damage-associated molecular patterns induce an early and exaggerated activation of innate immunity and a suppression of adaptive immunity. Severe complications are associated with a prolonged and dysregulated immune–inflammatory state. The current challenge in the management of THS patients is preventing organ injury, which currently has no etiological treatment available. Modulating the immune response is a potential therapeutic strategy for preventing the complications of THS. Mesenchymal stromal cells (MSCs) are multipotent cells found in a large number of adult tissues and used in clinical practice as therapeutic agents for immunomodulation and tissue repair. There is growing evidence that their efficiency is mainly attributed to the secretion of a wide range of bioactive molecules and extracellular vesicles (EVs). Indeed, different experimental studies revealed that MSC-derived EVs (MSC-EVs) could modulate local and systemic deleterious immune response. Therefore, these new cell-free therapeutic products, easily stored and available immediately, represent a tremendous opportunity in the emergency context of shock. In this review, the pathophysiological environment of THS and, in particular, the crosstalk between the immune system and organ function are described. The potential therapeutic benefits of MSCs or their EVs in treating THS are discussed based on the current knowledge. Understanding the key mechanisms of immune deregulation leading to organ damage is a crucial element in order to optimize the preparation of EVs and potentiate their therapeutic effect.

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Section: Immuno-properties Of Msc-evs and Mofmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

et al. 2021

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“…And more attractive thing is that BMSCs, one of the most important representations of MSCs, have been proved of signi cant treatment prospect for IBD [12,24]. The locations of IBD are mainly happened in gut, a unique immune organ, and it would be damaged when the balance between pro-in ammatory cells and anti-in ammatory cells was destroyed [25,26]. Some pro-in ammatory cells such as Th1 and Th17, differentiated by naive T cells, exert in uence on inducing and maintaining intestinal in ammation by secreting effector cytokines, while Tregs, another kind of cells derived from Naive T cells, are important anti-in ammatory cells which suppress the function of pro-in ammatory cells [27,28].…”

Section: Discussionmentioning

confidence: 99%

BMSCs improve TNBS-induced colitis in rats through inducing Tregs differentiation by expressing PD-L1

Gao

Fan

Shou

et al. 2021

Preprint

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Objective Bone marrow-derived mesenchymal stem cells (BMSCs) are a kind of stem cells with high differentiation potential and immunomodulatory ability, which has a broad prospect in the treatment of inflammatory bowel disease. The aim of this study is to investigate whether BMSCs could improve TNBS-induced colitis in Sprague-Dawley (SD) rats through inducing Tregs differentiation by expressing PD-L1. Methods BMSCs were isolated and identified by flow cytometry before being transfected with PD-L1 siRNA recombinant lentiviral vector. Then SD rats were randomly divided into 4 groups. Colitis induced by TNBS (sigma Aldrich) except normal group. On the fourth day of modeling, the rats in BMSCs control group and PD-L1 siRNA BMSCs group were injected with corresponding BMSCs through tail vein for 1 week, the dose was 5 × 106 cells. The normal group and model group were given the same volume of PBS. Results PD-L1 siRNA BMSCs and BMSCs could reach colon tissue in TNBS-induced colitis. BMSCs control group significantly improved the clinical symptoms and histopathological severity of TNBS induced colitis, but PD-L1 siRNA BMSCs group did not. We found that the percentage of Tregs in spleen and mesenteric lymph nodes decreased, the expression of PD-L1, IL10, PTEN was down-regulated, and the expression of p-Akt and p-mTOR was up-regulated in colon tissue after PD-L1 siRNA intervention. Conclusion This study suggested that BMSCs can induce the differentiation of Treg through inhibiting Akt/mTOR pathway by expressing PD-L1, which can significantly improve the symptoms and pathological damage of ulcerative colitis rats and affect the immune function.

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“…Many investigations have confirmed that the compound Sophora decoction can improve the immune function in UC and reduce colonic mucosal IkB-ɑ and NF-kB expression, thereby inhibiting TNF-ɑ and IL-6 expressions. Simultaneously, by inhibiting the activity of STAT6 and disrupting the balance of Th1/Th2 cells, it could improve the inflammatory state in UC and achieve a better therapeutic effect against UC [ 23 – 25 ]. Unlike the monomers, the compound acts through the multipathway and multitarget mechanism.…”

Section: Discussionmentioning

confidence: 99%

Differential Analysis of Serum Principal Components Treated with Compound Sophora Decoction and Related Compounds Based on High‐Resolution Mass Spectrometry (HRMS)

Sun

Zhang

Conghui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To compare the differences in the serum principal components in ulcerative colitis- (UC-) induced rats, treated with compound Sophora decoction, matrine, oxymatrine monomer mixture, and indirubin monomer, and to provide a modern scientific basis for elucidating the clinical efficacy of compound Sophora decoction for the treatment of UC. Methods. The serum samples of rats from each group were obtained after drug administration, and the serum principal components of each group were analyzed by high-resolution mass spectrometry. Agilent Eclipse XDB C18 chromatographic column (100 mm × 2.1 mm, 3.5 m) was used for separation. The mobile phase was water (A) and methanol (B) (0.1% formic acid) gradient elution, 0–3 min (B: 20%–40%), 3–10 min (B: 40%–54%), 10–25 min (B: 54%), 25–35 min (B: 54%–70%), 35–45 min (B: 70%–80%), 45–50 min (B: 80%), 50–60 min (B: 80%–100%), 70–72 min (B: 100%–20%), and 72–77 min (B: 20%); flow rate, 300 μL/min; column temperature, 40°C; and injection volume, 10 μL. ESI source was selected and scanned in the positive and negative ion modes. The scanning range was 70–1500 m/z; ion-source gas 1 (GS1): 55 psi; ion-source gas 2 (GS2): 60 psi; CUR: 30 psi; ion-source temperature (TEM): 550°C; ion-source voltage (ISVF) : 5500 V/−4500 V; decluster voltage (DP): 100 V; collision energy (CE): 35 V/−35 V; collision energy gain (CES) : 15 V/−15 V; and data acquisition mode: IDA. After the data from each group were imported into MarkView 1.3, the molecular weights and retention times of different substances were obtained and qualitatively analyzed by ChemSpider and PeakView 2.0. Results. In the negative ion mode, 26 differential compounds were identified in the compound Sophora decoction group (FFKST) compared to the model group (M), and 18 differential compounds were identified in the matrine and oxymatrine group (KST) compared to the model group (M). In the positive ion mode, 11 and 7 differential compounds were identified in the compound Sophora decoction group (FFKST) and the matrine and oxymatrine group (KST) compared to the model group (M), respectively. The responses of all compounds in each group were compared with each other. As the different principal component substances in the indirubin group (DYH) displayed little correlation with other groups, the different components in this group were not researched thoroughly. Conclusion. By comparing the differences in the serum principal components from each administration group, we found that the FFKST group exhibited enhanced synthesis of the serum principal components; however, the compound doses of matrine and oxymatrine monomers did not exhibit the same changes in the serum principal components of UC-induced rats. Finally, the traditional Chinese medicine compound is more advantageous than monomers.

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BMSC-EVs regulate Th17 cell differentiation in UC via H3K27me3

Cited by 28 publications

References 37 publications

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

BMSCs improve TNBS-induced colitis in rats through inducing Tregs differentiation by expressing PD-L1

Differential Analysis of Serum Principal Components Treated with Compound Sophora Decoction and Related Compounds Based on High‐Resolution Mass Spectrometry (HRMS)

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