M1 Macrophage Derived Exosomes Aggravate Experimental Autoimmune Neuritis via Modulating Th1 Response

Du, Tong; Yang, Chunlin; Ge, Meng‐Ru; Liu, Ying; Zhang, Peng; Li, Heng; Li, Xiaoli; Li, Tao; Liu, Yudong; Dou, Ying‐Chun; Yang, Bing; Duan, Rui‐Sheng

doi:10.3389/fimmu.2020.01603

Cited by 54 publications

(36 citation statements)

References 56 publications

(69 reference statements)

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“…Splenic T cells, B cells, and natural killer (NK) cells were purified using the method previously described [ 11 ]. In brief, the rat spleen was obtained and splenocytes were isolated after lysing red blood cells using RBC lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity

Zhang

Yang

et al. 2021

J Neuroinflammation

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Background Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear. Methods In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays. Results Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97–116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4+ T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells. Conclusions Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.

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Section: Methodsmentioning

confidence: 99%

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity

Zhang

Yang

et al. 2021

J Neuroinflammation

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“…Macrophages play either a pro-or antiinflammatory role in the different stages of GBS [19]. M1 cells can promote the expression of major histocompatibility complex II (MHC-II), adhesion molecules, reactive oxygen intermediates (ROI), amplify Th1 response via exosomes and inflammatory cytokines, resulting in inflammation, broken brood-nerve barrier (BNB) and demyelination [3,20]. In contrast, M2 macrophages exert a neuroprotective role in the pathogenicity of EAN [21].…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type

Shen

Chu

Lang

et al. 2021

Clinical and Experimental Immunology

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Guillain-Barré syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of the peripheral nervous system (PNS). Macrophages play a central role in its animal model, experimental autoimmune neuritis (EAN), which has been well accepted. Additionally, nuclear factor (NF)-κB inhibitors have been used to treat cancers and have shown beneficial effects. Here, we investigated the therapeutic effect of M2 macrophage and the NF-κB pathway's correlation with macrophage activation in EAN in C57BL/6 mice. We demonstrate that M2 macrophage transfusion could alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of proinflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.

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“…In contrast, under the stimulation of IL-4 and IL-13, M2 macrophages secrete mediators, such as IL-10 and transforming growth factor b, that contribute to the establishment of a tolerable microenvironment to exert anti-inflammatory and protumoral effects (69). Through experimental research, Du et al found that exosomes derived from M1 macrophages can directly regulate T cells, promoting Th1 cell differentiation (increasing the proportion) and effector functions (increasing IFN-g intensity) and increasing the production of IFN-g by CD8+ T cells (70). Moniek's data on the existence, induction, and plasticity of antigen-presenting cells in cervical cancer indicated that tumor-infiltrating Th1 cells could stimulate a tumor-rejecting environment by converting M2 macrophages to M1 macrophages (71).…”

Section: Discussionmentioning

confidence: 99%

“…Through experimental research, Du et al. found that exosomes derived from M1 macrophages can directly regulate T cells, promoting Th1 cell differentiation (increasing the proportion) and effector functions (increasing IFN-γ intensity) and increasing the production of IFN-γ by CD8+ T cells ( 70 ). Moniek’s data on the existence, induction, and plasticity of antigen-presenting cells in cervical cancer indicated that tumor-infiltrating Th1 cells could stimulate a tumor-rejecting environment by converting M2 macrophages to M1 macrophages ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

et al. 2021

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Age is a potential predictive marker for the prognosis of cancer patients treated with immune checkpoint inhibitors (ICIs), but the appropriate age cutoff point is still controversial. We aimed to explore the influence of different age cutoff points on the prediction of prognosis for patients receiving ICIs and explore the mechanism underlying the appropriate age cutoff point from the aspects of gene mutation and expression, immune cell infiltration and so on. We applied cutoff points of 50, 55, 60, 65, 70, and 75 years old to divide 1660 patients from the Memorial Sloan-Kettering Cancer Center (MSKCC) immunotherapy cohort into older and younger groups and performed survival analysis of the six subgroups. The results showed that older patients had better survival than younger patients in accordance with the cutoff point of 50 years old [median overall survival (OS) (95% CI): 13.0 (10.5-15.5) months vs. 20.0 (16.7-23.3) months; p=0.002; unadjusted hazard ratio (HR) (95% CI): 0.77 (0.65-0.91)], whereas no significant difference was observed with other cutoff points. Further analysis of The Cancer Genome Atlas (TCGA) database and the MSKCC immunotherapy cohort data showed that the tumor mutation burden (TMB), neoantigen load (NAL), DNA damage response and repair (DDR) pathway mutation status, mutation frequencies of most genes (except IDH1, BRAF and ATRX), the expression of most immune-related genes and the degree of infiltration of most immune cells (such as CD8+ T cells and M1 macrophages) were higher in the elderly group (aged ≥50 years).

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M1 Macrophage Derived Exosomes Aggravate Experimental Autoimmune Neuritis via Modulating Th1 Response

Cited by 54 publications

References 56 publications

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

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