Neurological disorders (NDs) are one of the leading causes of global death. A sustained neuroinflammatory response has been reported to be associated with the pathogenesis of multiple NDs, including Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and major depressive disorder (MDD). Accumulating evidence shows that the recruitment of abundant lymphocytes in the central nervous system may contribute to promoting the development and progress of inflammation in neurological disorders. As one subset of T lymphocytes, CD4⁺ T cells have a critical impact on the inflammation of neurological disorders. T helper (Th) 17 is one of the most studied CD4⁺ Th subpopulations that produces cytokines (e.g., IL-17A, IL-23, IL-21, IL-6, and IFN-γ), leading to the abnormal neuroinflammatory response including the excessive activation of microglia and the recruitment of other immune cell types. All these factors are involved in several neurological disorders. However, the possible mechanisms of Th17 cells and their associated cytokines in the immunopathology of the abovementioned neurological disorders have not been clarified completely. This review will summarize the mechanisms by which encephalitogenic inflammatory Th17 cells and their related cytokines strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes in NDs. Finally, the potential therapeutic prospects of Th17 cells and their cytokines in NDs will also be discussed.

Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in IBD. In this study, IBD expression profiles were screened from public Gene Expression Omnibus datasets. Functional enrichment analysis revealed that IBD-related specific functions were associated with immune pathways. Five MMPS-related disease markers, namely MMP-9, CD160, PTGDS, SLC26A8, and TLR5, were selected by machine learning and the correlation between each marker and immune cells was evaluated. We then induced colitis in C57 mice using sodium dextran sulfate and validated model construction through HE staining of the mouse colon. WB and immunofluorescence experiments confirmed that the expression levels of MMP-9, PTGDS, SLC26A8, and CD160 in colitis were significantly increased, whereas that of TLR5 were decreased. Flow cytometry analysis revealed that MMPs regulate intestinal inflammation and immunity mainly through CD8 in colitis. Our findings reveal that MMPs play a crucial role in the pathogenesis of IBD and are related to the infiltration of immune cells, suggesting that MMPs may promote the development of IBD by activating immune infiltration and the immune response. This study provides insights for further studies on the occurrence and development of IBD.

Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high‑density lipoprotein (HDL) decreases inflammatory responses via the apoM‑sphingosine‑1‑phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM‑/‑) were employed to investigate the effects of ApoM on the expression of interleukin‑1β (IL‑1β), monocyte chemotactic protein‑1 (MCP‑1), S1P receptor‑1 (S1PR1) and 3β‑hydroxysterol Δ‑24‑reductase (DHCR24), as compared with in wild‑type mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (rec‑apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor‑α (TNF‑α), in order to investigate the effects of ApoM on IL‑1β and MCP‑1. The results demonstrated that the mRNA expression levels of IL‑1β and MCP‑1 were significantly higher in the liver following administration of lipopolysaccharide in apoM‑/‑ mice compared with in apoM+/+ mice. In cell culture experiments, when cells were pre‑cultured with rec‑apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL‑1β and MCP‑1 following TNF‑α treatment compared with in normal apoM‑expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL‑1β and MCP‑1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport‑1 (BLT‑1), in apoMTg cells prior to TNF‑α treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT‑1 prior to TNF‑α treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways.

The fetal origins of adult disease hypothesis proposes that a variety of adverse stimuli during critical development stages can impair the structure and function of fetal organs, thereby increasing the risk of disease later in life. Iron affects fetal growth and development by facilitating oxygen and electron transport and by serving as a cofactor for enzymes that affect enzyme activity. Fetal iron deficiency (ID) can result from various factors during pregnancy, including inadequate maternal iron intake, maternal obesity, diabetes, smoking, prenatal stress, and prenatal alcohol exposure. These conditions disrupt fetal brain development and are associated with neurological disorders in offspring, such as cognitive impairment, anxiety, depression, schizophrenia, and autism. However, the mechanisms by which maternal iron deficiency leads to abnormal neurological development, as well as cognitive impairment and psychiatric disorders in the offspring, remain unknown. In this review, we summarize the causes of prenatal iron deficiency, the effects of iron deficiency on brain development and behavioral phenotypes, and the potential molecular mechanisms.