TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ

Li, Ruixue; Wang, Renyong; Zhong, Shijie; Asghar, Farhan; Li, Tiehan; Zhu, Li; Zhu, Hong

doi:10.1515/biol-2021-0118

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…It has been shown that TGF‐β1 secreted from mesenchymal stem cells functions in various aspects of the immune system. TGF‐β1 inhibits T cell, B cell, and NK cell function (Li et al., 2021; Niu et al., 2017). Hence, IWP‐2‐promoted TGF‐β1 mRNA expression in both normal and in vitro inflammation conditions could result in immunomodulatory effects.…”

Section: Discussionmentioning

confidence: 99%

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

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AimTo investigate the effect of IWP‐2, Wnt inhibitor, on human dental pulp stem cells (hDPSCs) responses.MethodologyhDPSCs were isolated from human dental pulp tissues. Cells were treated with 25 μM IWP‐2 for 24 h, and subsequently, the gene expression profile was examined using high‐throughput RNA sequencing. The mRNA expression was analysed using qPCR. The effect of IWP‐2 was investigated in both normal and LPS‐induced hDPSCs (inflamed hDPSCs). CD4+ T cells and CD14+ monocyte‐derived macrophages were cultured with conditioned media of IWP‐2 treated hDPSCs to observe the immunosuppressive property.ResultsRNA sequencing indicated that IWP‐2 significantly downregulated several KEGG pathways, including cytokine‐cytokine receptor interaction, IL‐17 signalling pathway, and TNF signalling pathway. In both normal and inflamed conditions, IWP‐2 markedly upregulated TGFB1 mRNA expression while the mRNA expression of pro‐inflammatory cytokines, TNFA, IL1B, IFNG, and IL6, was inhibited. In the inhibition experiment, the pretreatment with p38, MAPK, or PI3K inhibitors abolished the effects of IWP‐2 in LPS‐induced inflammation. In terms of immune cells, IWP‐2‐treated‐inflamed hDPSCs conditioned media attenuated T cell proliferation and regulated regulatory T cell differentiation. In addition, the migratory property of macrophage was decreased after being exposed to IWP‐2‐treated inflamed hDPSCs conditioned media.ConclusionIWP‐2 suppressed inflammatory cytokine expression in both normal and inflamed hDPSCs. Moreover, hDPSCs exerted the immunosuppressive property after IWP‐2 treatment. These results suggest the role of Wnt in inflammatory responses and immunomodulation in dental pulp tissues.

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Section: Discussionmentioning

confidence: 99%

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

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“…Despite the critical role of TGFβ in the modulation of the immunosuppressive ability of MSCs (27), there are conflicting arguments among researchers. Li et al demonstrated the immunosuppression potential of TGFβ1 overexpressed MSCs on co-cultured T lymphocytes (51). Conversely, Xu et al showed that TGFβ could decrease the immunosuppression capacity of MSCs (52).…”

Section: Discussionmentioning

confidence: 99%

TGFβ1-Pretreated Exosomes of Wharton Jelly Mesenchymal Stem Cell as a Therapeutic Strategy for Improving Liver Fibrosis

et al. 2022

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Background: Mesenchymal stem cells (MSCs) are the most promising tools for cell treatment and human tissue regeneration, e.g., in liver fibrosis. Mesenchymal stem cells repair tissue damage through paracrine mediators such as exosomes. Types and concentrations of inflammatory mediators, including transforming growth factor-beta (TGFβ1), in MSCs microenvironment can affect MSCs’ function and therapeutic potency. Objectives: This experimental study aimed to explore the effects of Wharton jelly MSCs (WJ-MSCs) exosomes on fibrotic gene expression and Smad2/3 phosphorylation (phospho-Smad2/3 (p-Smad2/3)). Moreover, we further investigated whether WJ-MSCs pretreatment with different concentrations of TGFβ1 changes the anti-fibrotic properties of their exosomes. Methods: After isolation from the umbilical cord, WJ-MSCs were characterized by observing differentiation and measuring surface biomarkers using flowcytometry. The WJ-MSC-derived exosomes were extracted and identified using transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. Real-time PCR and western blot for extracellular matrix (ECM) and p-Smad2/3 expression detection were used to investigate the effect of exosomes from untreated and TGFβ1-pretreated WJ-MSCs on activated hepatic stellate cells (HSCs). Results: Phospho-Smad2/3, α-smooth muscle actin (α-SMA), and collagen1α1 levels were enhanced following treatment with TGFβ1, whereas E-cadherin was decreased. However, the outcomes were reversed after treatment with WJ-MSC-derived exosomes. Exosomes from TGFβ1-pretreated WJ-MSCs induced a significant decrease in p-Smad2/3 levels in activated HSCs, accompanied by the upregulation of E-cadherin gene expression and downregulation of α-SMA and collagen1α1 when compared to untreated WJ-MSC-derived exosomes. The p-Smad2/3 proteins were significantly decreased (fold change: 0.23, P-value < 0.0001) after exposure to low-dose TGFβ1-pretreated WJ-MSC-derived exosomes (0.1 ng/mL), showing the best effect on activated HSCs. Conclusions: Exosomes derived from untreated WJ-MSCs could regress TGFβ-Smad2/3 signaling and the expression of fibrotic markers in activated LX-2 cells. However, these effects were significantly profound with applying exosomes derived from 0.1 ng/mL TGFβ-pretreated WJ-MSCs. We also observed the dose-response effects of TGFβ on WJ-MSCs-derived exosomes. Therefore, exosomes derived from TGFβ-pretreated WJ-MSCs may be critical in improving fibrosis and benefit liver fibrosis patients.

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“…Tregs are generated when antigens are presented by DCs to lymphocytes in the GALT during the eubiotic state ( Lathrop et al, 2011 ). Tregs produce anti-inflammatory cytokines, such as IL-10 and TGFβ, which are responsible for the inhibition of proinflammatory cytokine production, switching the immune response from Th1/Th17-dependent to Th2-dependent ( Li et al, 2021 ), and therefore quenching the immune reaction and promoting the repair process in the damaged tissue ( Mingomataj and Bakiri, 2016 ). Induced Tregs may also translocate into circulation and inhibit the inflammatory responses in the organism ( Weiner and Wu, 2011 ).…”

Section: Gut-brain Axis (Gba)mentioning

confidence: 99%

Communication of gut microbiota and brain via immune and neuroendocrine signaling

2023

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The gastrointestinal tract of the human is inhabited by about 5 × 1013 bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).

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TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ

Cited by 7 publications

References 30 publications

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

TGFβ1-Pretreated Exosomes of Wharton Jelly Mesenchymal Stem Cell as a Therapeutic Strategy for Improving Liver Fibrosis

Communication of gut microbiota and brain via immune and neuroendocrine signaling

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