The balance between Treg and TH<sub>17</sub> cells: CD11b and interleukin‐6

Garbers, Christoph; Rose-John, Stefan

doi:10.1002/eji.201746988

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…Normally, TGF‐β alone induces Naïve CD4 + T cells to differentiate into Treg cells. Inflammation could trigger IL‐6 overproduction, which in turn induce Th17 cell differentiation in collaboration with TGF‐β . IL‐6 binds to a receptor complex consisting of the ligand‐binding subunit IL‐6R and the signaling subunit gp130 and subsequently activates JAK/STAT3 signaling that is essential for Th17 cell development .…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

et al. 2019

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The purpose of this study was to explore the mechanism by which human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)-derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). hUCB-MSCs-derived exosomes were administrated into hepatic IRI mice or cocultured with naïve CD4 + T cells exposed to hepatic hypoxia/reoxygenation microenvironment. Hepatic function was assessed by determining serum transaminases. Histological changes were observed using hematoxylin and eosin staining. The proportion of T helper 17 (Th17) and regulatory T (Treg) cells were analyzed by flow cytometry. The concentration of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The interaction between miR-1246 and interleukin 6 (IL-6) signal transducer (also known as gp130) was verified by luciferase activity assay. The miR-1246 expression, Th17/ Treg-related genes, and gp130-signal transducer and activator of transcription 3 (STAT3) pathway were detected by quantitative real-time polymerase chain reaction and western blotting. hUCB-MSCs-derived exosomes ameliorated IRI-induced hepatic dysfunction and decreased Th17/Treg ratio in CD4 + T cells in vitro, whereas treatment of hUCB-MSCs with miR-1246 inhibitor showed opposite effects, which was mediated via the IL-6-gp130-STAT3 pathway. hUCB-MSCs-derived exosomes could alleviate hepatic IRI through modulating the balance between Tregs and Th17 cells via miR-1246-mediated IL-6-gp130-STAT3 axis. K E Y W O R D Sexosomes, gp130, hepatic injury, ischemia/reperfusion, miR-1246

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Section: Discussionmentioning

confidence: 99%

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

et al. 2019

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“…Notably, recent research by Garbers et al has shed light on the role of CD11b in this context. They demonstrated that CD11b compromises the in ammatory induction of IL-6, resulting in reduced IL-6 secretion and a higher abundance of Treg cells compared to Th17 cells (44). Conversely, the absence of CD11b leads to heightened IL-6 secretion and an increased prevalence of Th17 cells over Treg cells (45).…”

Section: Discussionmentioning

confidence: 99%

Uncovering Causal Associations of Immune Cells with Rheumatoid Arthritis: A Mendelian Randomization Study

王,

Su,

Zhang

et al. 2024

Preprint

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Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint damage and functional limitations, often accompanied by comorbidities. While the impact of immune cells on the development of RA is recognized, the precise causal relationships with various immunophenotypes are yet to be fully understood. Methods We performed a comprehensive two-sample Mendelian randomization (MR) study to explore the associations between immunophenotypes and RA. Utilizing publicly available genetic datasets, we examined causal links involving 731 immune cell traits, categorized into four groups: relative cell counts (RC), median fluorescence intensities (MFI), morphological parameters (MP), and absolute cell counts (AC). Extensive sensitivity analyses were carried out to validate the robustness of our results. These analyses aimed to assess heterogeneity and investigate the potential influence of horizontal pleiotropy. Results After applying FDR correction, two specific immunophenotypes were found to be associated with RA: CD33dim HLA-DR + CD11b+ %CD33dim HLA-DR + and CD33dimHLA-DR + CD11b-%CD33dimHLA-DR+. The odds ratios (ORs) for RA risk forthese immunophenotypes, calculated using the inverse variance weighting(IVW) method, were 0.970 (95% CI = 0.955–0.985, P = 1.09×10− 4, PFDR = 0.058) and 1.027 (95% CI = 1.011–1.042, P = 5.05×10− 4, PFDR = 0.074), respectively. In contrast, without FDR correction, six additional immunophenotypes showed significant associations with RA: CD14 on CD33dim HLA-DR + CD11b+, CD16 on CD14 + CD16 + monocytes, CD11b on basophils, CD3 on TD CD4+, PDL-1 on CD14- CD16 + monocytes, and CD4 on HLA-DR + CD4+. Of these, the first two were linked to increased RA risk, while the latter four exhibited protective characteristics. Conclusions This study highlights a strong genetic link between immune cell profiles and RA, illuminating potential targets for innovative therapeutic strategies.

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“…45 Recent studies in murine collagen-induced arthritis model showed that neutralizing antibody against the IL-6R significantly reduced the disease score by reducing the percentage of Th17 cells and increasing the percentage of Treg cells. 47 A study has shown that released HSP70 from myeloma cells leads to increase the secretion of IL-6 from stromal cells. 48 As well as other research has shown that exogenous HSP70 increases the IL-6 by affecting monocytes by activating the pathway dependent on CD14 and intracellular calcium.…”

Section: Discussionmentioning

confidence: 99%

Carbenoxolone Could Deteriorate Streptozotocin-induced Diabetes through Induction of Heat Shock Protein 70 and IFN-γ in C57BL/6 Mice

Rasouli

Jafari-Khataylou

Ashrafihelan

2019

IJAAI

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Type 1 diabetes (T1D), a spontaneous autoimmune disease, is associated with destruction of insulin-producing β-cells in the pancreas. Since some heat shock proteins (HSP), such as HSP70 exert a protective effect in both tissues and cells, the present study was conducted to elucidate the effects of carbenoxolone (CBX) as an HSP70 inducer on T1D. The disease was induced in male C57BL/6 mice using streptozotocin (STZ) and subjects were allocated to therapeutic 1 and therapeutic 2 groups, as well as negative and positive control groups. The treated mice (therapeutic 1 and therapeutic 2 groups) received 50 mg/kg CBX intraperitoneally every 24 hours, in the therapeutic 1 group the drug was injected before and after disease induction whereas in the therapeutic 2 group the drug was injected only after disease induction. Serum fasting blood sugar (FBS) level, cytokines production (Interferon-gamma (IFN-γ), Interleukin 10 (IL-10), and IL-17), serum HSP70 level and CD4+CD25+Foxp3+ regulatory T cell (Treg) frequency measurements were outperformed 14 days after the last STZ injection. Our results showed that in the treated groups, serum HSP70, IFN-γ, and IL-17 levels were increased in contrast to the untreated groups. The IL-10 level was markedly decreased in comparison to untreated diabetic mice (p<0.05). Moreover, it was found that the frequency of Tregs in treated mice was lower in comparison to the untreated mice but the difference was not significant (p>0.05). Our results confirm that CBX might through HSP70 induction, followed by increasing IFN-γ level leads to suppression of IL-10 production in diabetic mice resulted in toxic effects on pancreatic islet beta cells and deteriorating of disease.

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The balance between Treg and TH₁₇ cells: CD11b and interleukin‐6

Cited by 4 publications

References 29 publications

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

Uncovering Causal Associations of Immune Cells with Rheumatoid Arthritis: A Mendelian Randomization Study

Carbenoxolone Could Deteriorate Streptozotocin-induced Diabetes through Induction of Heat Shock Protein 70 and IFN-γ in C57BL/6 Mice

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The balance between Treg and TH17 cells: CD11b and interleukin‐6

Cited by 4 publications

References 29 publications

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance

Uncovering Causal Associations of Immune Cells with Rheumatoid Arthritis: A Mendelian Randomization Study

Carbenoxolone Could Deteriorate Streptozotocin-induced Diabetes through Induction of Heat Shock Protein 70 and IFN-γ in C57BL/6 Mice

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The balance between Treg and TH₁₇ cells: CD11b and interleukin‐6