Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells

Terraza-Aguirre, Claudia; Campos‐Mora, Mauricio; Elizondo‐Vega, Roberto; Contreras-López, Rafael; Luz‐Crawford, Patricia; Jørgensen, Christian; Djouad, Farida

doi:10.3390/cells9071660

Cited by 29 publications

(23 citation statements)

References 177 publications

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Section: Pge2 and Lxa4 Interact To Induce Resolution Of Inflammationmentioning

confidence: 99%

“…In general, it is believed that PGE2 is a pro-inflammatory molecule. However, several studies suggest that PGE2 is essential to initiate or trigger anti-inflammatory process [ 111 , 112 , 113 ]. This paradoxical yet beneficial property of PGE2 can be attributed to its ability to bind to different types of PGE2 receptors (EPs).…”

Section: Pge2 and Lxa4 Interact To Induce Resolution Of Inflammatmentioning

confidence: 99%

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“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Das

2021

Biomolecules

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Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hypertension, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these conditions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. SIRT1 activation prevents aging. Of all the SIRTs, SIRT6 is critical for intermediary metabolism and genomic stability. SIRT6-deficient mice show shortened lifespan, defects in DNA repair and have a high incidence of cancer due to oncogene activation. SIRT6 overexpression lowers LDL and triglyceride level, improves glucose tolerance, and increases lifespan of mice in addition to its anti-inflammatory effects at the transcriptional level. PUFAs and their anti-inflammatory metabolites influence the activity of SIRT6 and other SIRTs and thus, bring about their actions on metabolism, inflammation, and genome maintenance. GLA, DGLA, AA, EPA and DHA and prostaglandin E2 (PGE2), lipoxin A4 (LXA4) (pro- and anti-inflammatory metabolites of AA respectively) activate/suppress various SIRTs (SIRt1 SIRT2, SIRT3, SIRT4, SIRT5, SIRT6), PPAR-γ, PARP, p53, SREBP1, intracellular cAMP content, PKA activity and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α). This implies that changes in the metabolism of bioactive lipids as a result of altered activities of desaturases, COX-2 and 5-, 12-, 15-LOX (cyclo-oxygenase and lipoxygenases respectively) may have a critical role in determining cell age and development of several aging associated diseases and genomic stability and gene and oncogene activation. Thus, methods designed to maintain homeostasis of bioactive lipids (GLA, DGLA, AA, EPA, DHA, PGE2, LXA4) may arrest aging process and associated metabolic abnormalities.

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Section: Pge2 and Lxa4 Interact To Induce Resolution Of Inflammationmentioning

confidence: 99%

Section: Pge2 and Lxa4 Interact To Induce Resolution Of Inflammatmentioning

confidence: 99%

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Das

2021

Biomolecules

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“…These findings may explain the phenomenon that IDO-mediated tryptophan exhaustion caused mTORC1 (as a nutrient sensor) inhibition, which further suppressed Th17 number and function but promoted Treg generation. Moreover, IDO depletion or tryptophan supplement reversed the effects (9,61,62,64).…”

Section: Msc Inhibition On Mtor Signalingmentioning

confidence: 93%

“…Mechanistically, MSC regulates the balance between Th17 and Treg predominantly via indoleamine 2, 3-dioxgenase (IDO) and TGF-b secretions as well as other mechanisms, which mimic the rapamycin effect of inhibiting mTOR, including mTOR complex 1 (mTORC1) and 2 (mTORC2) (8,9,(60)(61)(62)(63)(64)(65). Accumulating evidence indicates that mTOR, a serine/threonine kinase, acts as a key regulator of metabolic programmers and signaling pathways in CD4 + T cell differentiation (62,66,67).…”

Section: Msc-mediated Mtor Inhibition Regulating Th17/treg Axismentioning

confidence: 99%

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Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis

Luo

Guo

Zhang³

et al. 2021

Front. Immunol.

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The increase in T helper 17 cell (Th17)-mediated pro-inflammatory response and decrease in regulatory T cell (Treg)-mediated anti-inflammatory effect aggravate renal tubular epithelial cell (RTEC) injury. However, increasing evidence indicated that mesenchymal stem cell (MSC) possessed the ability to control the imbalance between Th17 and Treg. Given that Th17 and Treg are derived from a common CD4+ T cell precursor, we summarize the current knowledge of MSC-mediated inhibition of the mammalian target of rapamycin (mTOR), which is a master regulator of CD4+ T cell polarization. During CD4+ T cell differentiation, mTOR signaling mediates Th17 and Treg differentiation via hypoxia-inducible factor-1α (HIF-1α)-dependent metabolic regulation and signaling pathway, as well as mTOR-mediated phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5. Through interfering with mTOR signaling, MSC restrains CD4+ T cell differentiation into Th17, but in turn promotes Treg generation. Thus, this review indicates that MSC-mediated Th17-to-Treg polarization is expected to act as new immunotherapy for kidney injury.

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Evaluation of the relationship between mesenchymal stem cells and immune system in vitro conditions

et al. 2023

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Determination of the immunomodulatory properties of mesenchymal stem cells (MSCs) is necessary before clinical applications. In this study, it was aimed to determine the effect of MSCs on cytokines secreted by the immune system cells.Intracellular cytokine levels (Interleukin-4 (IL-4), Interferon-γ (IFN-γ), and Interleukin-17 (IL-17)) detected by ow cytometry before and after co-culture between peripheral blood mononuclear cells (PBMCs) and MCSs. At the same time, supernatant cytokine levels were measured using the ELISA. In our study, MSCs were isolated from cord blood (CB) and Wharton's Jelly (WJ), and their surface markers (CD44 (100%), CD73 (99.6%), CD90 (100%), CD105 ( 88%))shown by ow cytometry method. Both CB-MSCs and WJ-MSCs were used in co-culture MSC/PBMC ratios of 1/5 and 1/10, incubation times of 24 hours and 72 hours.In the present study, when we compared co-cultures of CB-MSC or WJ-MSC with PBMCs, intracellular levels of cytokines IFN-γ, IL-17 (pro-in amatory) and IL-4 (anti-in amatory) were increased and supernatant levels were decreased signi cantly (p < 0.05). The level of TGF-β (anti-in amatory) was signi cantly decreased for both CB-MSC and WJ-MSC in supernatant (p < 0.05).It was investigated the pro-in ammatory and anti-in ammatory effects of CB-MSCs and WJ-MSCs on PBMCs with the obtained results. According to the results, MSCs demonstrated different immunologic effects after the incubation time and ratios For further studies, it should be known between interaction of MSCs and immune system.

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Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells

Cited by 29 publications

References 177 publications

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis

Evaluation of the relationship between mesenchymal stem cells and immune system in vitro conditions

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