Immunoglobulin (Ig) is a critical molecule in the body's defense against foreign substances such as bacteria and viruses. While traditionally considered B cell specific, studies have reported that Ig is also expressed by non-B cells. However, it is not known to what extent Ig is expressed in the brain and which type of variable regions are expressed. In this study, we elucidated the expression profile of Igs from embryonic to adult stages using single-cell RNA sequencing data and Ig repertoire analysis. Our results revealed that microglia express Ighm transcripts from embryonic to adult stages. These transcripts contain the upstream region of the Ighj region. In addition, Ighm is expressed in the layer 6 corticothalamic neurons, some of which co-express Ighg2c in the adult brain. In particular, we were able to generate a comprehensive profile of Ig variable region expression from embryonic to adult stages. Furthermore, the response of Ighm expression in microglia to lipopolysaccharide is markedly different from that in B cells, suggesting a novel, brain-specific role for the Ig gene, distinct from its classical function in the immune system.
© 2025. The Author(s).

Abstract Immunoglobulin (Ig) is a critical molecule in the body’s defense against foreign substances such as bacteria and viruses. While traditionally considered B cell specific, studies have reported that Ig is also expressed by non-B cells. However, it is not known to what extent Ig is expressed in the brain and which type of variable regions are expressed. In this study, we elucidated the expression profile of Igs from embryonic to adult stages using single-cell RNA sequencing data and Ig repertoire analysis. Our results revealed that microglia express Ighm transcripts from embryonic to adult stages. These transcripts contain the upstream region of the Ighj region. In addition, Ighm is expressed in the layer 6 corticothalamic neurons, some of which co-express Ighg2c in the adult brain. In particular, we were able to generate a comprehensive profile of Ig variable region expression from embryonic to adult stages. Furthermore, the response of Ighm expression in microglia to lipopolysaccharide is markedly different from that in B cells, suggesting a novel, brain-specific role for the Ig gene, distinct from its classical function in the immune system.

Magnesium sulfate (MgSO4) possesses the advantages of being readily accessible, cost-effective, and having low toxicity. It has potential applications as a neuroprotective agent. The mechanisms underlying the effects of Mg2+ treatment on depression and its neuroprotective properties remain poorly elucidated.
In this study, we employed chronic mild unpredictable stress (CMS)-induced mice were orally administered with MgSO4 or pioglitazone. The CMS-induced depressive-like behaviors of mice were monitored. After sacrifice, the levels of Mg2+ and inflammatory cytokines were observed. Blood-brain barrier (BBB) permeability and the M1-to-M2 shift of microglia in mouse hippocampus were detected. The expression of proteins in IKK/NF-κB and NLRP3 inflammasome signal pathway were analyzed.
We found that CMS induced depressive-like behaviors as well as hypomagnesemia in mice, which were accompanied with hypersecretion of inflammatory cytokines in hippocampus of mice. These animals induced by CMS exhibited hippocampal neuroinflammation characterized by an elevated number of Iba+ microglia with enlarged cell bodies and increased branching structures. In CMS-induced mice, MgSO4 alleviated CMS-induced depressive-like behaviors and hypomagnesemia, reduced the levels of inflammatory cytokines in both serum and hippocampus, decreased the number of Iba+ microglia, modulated microglia polarization and repaired the BBB damage. MgSO4 also significantly facilitates the M1-to-M2 shift in CMS-induced mouse hippocampus and lipopolysaccharide (LPS)-induced BV2 microglia. Mechanically, we found that MgSO4 inhibited microglia activation and BBB damage, possibly by suppressing IKK/NF-κB and NLRP3 inflammasome signaling pathways.
Our findings showed that MgSO4 supplementation played an active role in the prevention and treatment of depression.
Copyright © 2025 Wang, Hu, Li, Hu, Zhang, Qiao, Tang and Wang.

The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-κB, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male- than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation.
Copyright: © 2025 Honecker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Intervertebral disc degeneration (IDD) is a degenerative spinal condition characterized by disc structural damage, narrowing of joint spaces, and nerve root compression, significantly reducing patients' quality of life. To address this challenge, a novel therapeutic strategy was developed using cellulose supramolecular hydrogel as a carrier to deliver IL4I1-modified MΦ membrane biomimetic nanoparticles (CHG@IL4I1-MNPs) to target tissues. This hydrogel exhibits excellent biocompatibility and mechanical properties while enabling sustained drug release in the degenerative disc microenvironment, enhancing therapeutic outcomes. CHG@IL4I1-MNPs effectively regulate MΦ polarization by promoting M2 MΦ activation, thereby improving immune microenvironment balance. Animal studies demonstrated that CHG@IL4I1-MNPs alleviated symptoms of IDD, reduced inflammation, and supported tissue repair, highlighting its potential to reduce reliance on long-term medication and improve quality of life. The strategy uniquely combines nanoparticle technology with immunomodulation, achieving precise targeting of MΦs. Beyond IDD, this approach offers potential applications in other immune-related diseases, providing a versatile platform for nanomedicine. This study introduces an innovative method to treat IDD and advances the integration of immunotherapy and nanotechnology, offering both clinical benefits and new directions for future research. These findings hold strong potential for improving patient outcomes and expanding treatment options for related diseases.
© 2025. The Author(s).