Extracellular vesicles (EVs) are nanometer-sized and membrane-bound vesicles, including exosomes and microvesicles. EVs can deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types including stem/progenitor cells. Stem/progenitor cell-derived EVs have been identified to exert immunomodulatory effects on target cells through transferring protein molecules as well as regulatory effects on the phenotype of target cells through fusion with the target cells membrane and/or through direct endocytosis by target cells to transfer nucleic acid substances (such as mRNA, miRNA) to the target cells. In both human and animal models, the use of stem/progenitor cells (such as bone marrow mesenchymal stromal cells) has been shown to promote the recovery of kidney diseases such as acute kidney injury and chronic kidney disease. Stem/progenitor cell-derived extracellular vesicles are an important mechanism by which stem/progenitor cells might repair kidney injury. Here, this review will discuss the latest advances concerning the application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases, including the aspects as follows: anti-inflammatory, proliferation-promoting and anti-apoptotic, proangiogenic, antifibrotic and renal cancer progression-promoting. Therefore, stem/progenitor cell-derived extracellular vesicles may be a promising treatment tool for renal diseases.

Abnormal CD4T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4 T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4 T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4T cell-mediated immune responses in MG.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.

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Recently, microRNAs (miRNAs) have been reported to play crucial roles in immune responses and other biological processes, but the role of miR‐181a in myasthenia gravis (MG) has been relatively less studied. We found that miR‐181a was downregulated in the peripheral blood mononuclear cells (PBMCs) of MG patients and was associated with QMGs and anti‐AChR Ab levels. In vitro experiments indicated that miR‐181a was involved in the modulation of CD4+ T cell activation and plasticity and that miR‐181a decreased the expression level of the Th1‐related transcription factor T‐bet and the Th17‐related transcription factor RORγt. In the in vivo experiment, miR‐181a treatment alleviated experimental autoimmune myasthenia gravis (EAMG) symptoms and affected both CD4+ T cell differentiation and the production of anti‐AChR antibodies. Moreover, in this study, we also found that IL‐2 was regulated by miR‐181a and that its expression level showed a strong negative correlation with miR‐181a levels in MG patients. To illustrate that the expression levels of both IL‐2 and miR‐181a were sensitive to immunomodulatory therapy treatment in MG, we found that IL‐2 and miR‐181a were correlated with clinical severity. These findings demonstrate that miR‐181a can contribute to the pathogenesis of MG by regulating IL‐2 expression.This article is protected by copyright. All rights reserved

Immune checkpoint inhibitors (ICIs) are being used in patients with various advanced malignancies, and patient outcomes have improved considerably. Although ICIs can effectively treat tumors, 30–60% of patients experience immune-related adverse events (irAEs). Autoimmune encephalitis (AE) is a rare irAE that has become a novel topic in neuroimmunology and has received increasing attention in recent years. Herein, we report a rare case of GAD65-antibody–associated AE after metastatic small cell lung cancer treatment with pembrolizumab. The patient received IVIg therapy for AE and continuous pembrolizumab therapy without suspension of tumor treatment. At 1 year follow-up, both the patient’s AE symptoms and tumors were stable. We consider that the treatment of ICI-associated AE should be more individualized with prudent decision-making and should balance the tumor progression and AE treatment. In addition, we have also comprehensively reviewed the literature of ICI-associated AE, and summarized the clinical features, treatment, and prognosis of AE caused by ICI, thus broadening our understanding of the neurological complications caused by ICI.

Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the anti-IgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in anti-IgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.

Background Amyloid positron emission tomography (PET) can measure in-vivo demyelination in patients with multiple sclerosis (MS). However, the value of 18 F-labeled amyloid PET tracer, 18 F-florbetapir in the longitudinal study for monitoring myelin loss and recovery has not been confirmed. Methods From March 2019 to September 2020, twenty-three patients with MS and nine healthy controls (HCs) underwent a hybrid PET/MRI at baseline and expanded disability status scale (EDSS) assessment, and eight of 23 patients further underwent follow-up PET/MRI. The distribution volume ratio (DVR) and standard uptake value ratio (SUVR) of 18 F-florbetapir in damaged white matter (DWM) and normal-appearance white matter (NAWM) were obtained from dynamic and static PET acquisition. Diffusion tensor imaging-derived parameters were also calculated. Data were expressed as mean ± standard deviation with 99% confidence interval (99%CI). Finding The mean DVR (1.08 ± 0.12, 99%CI [1.02 ~ 1.14]) but not the mean SUVR of DWM lesions was lower than that of NAWM in patients with MS (1.25 ± 0.10, 99%CI [1.20 ~ 1.31]) and HCs (1.29 ± 0.08, 99%CI [1.23 ~ 1.36]). A trend toward lower mean fractional anisotropy (374.95 ± 45.30 vs. 419.07 ± 4.83) and higher mean radial diffusivity (0.45 ± 0.05 vs. 0.40 ± 0.01) of NAWM in patients with MS than those in HCs was found. DVR decreased in DWM lesions with higher MD (rho = -0.261, 99%CI [-0.362 ~ -0.144]), higher AD (rho = -0.200, 99%CI [-0.318 ~ -0.070]) and higher RD (rho = -0.198, 99%CI [-0.313 ~ -0.075]). Patients’ EDSS scores were reduced ( B = 0.04, 99%CI [-0.005 ~ 0.084]) with decreased index of global demyelination in the longitudinal study. Interpretation Our exploratory study suggests that dynamic 18 F-florbetapir PET/MRI may be a very promising tool for quantitatively monitoring myelin loss and recovery in patients with MS. Funding Shanghai Pujiang Program, Shanghai Municipal Key Clinical Specialty, Shanghai Shuguang Plan Project, Shanghai Health and Family Planning Commission Research Project, Clinical Research Plan of SHDC, French-Chinese program "Xu Guangqi".