The occurrence of B cell aggregates within the central nervous system (CNS) has prompted the investigation of the potential sources of pathogenic B cell and T cell responses in a subgroup of secondary progressive multiple sclerosis (MS) patients. Nevertheless, the expression profile of molecules associated with these aggregates and their role in aggregate development and persistence is poorly described. Here, we focused on the expression pattern of osteopontin (OPN), which is a well-described cytokine, in MS brain tissue. Autopsied brain sections from MS cases with and without B cell pathology were screened for the presence of CD20⁺ B cell aggregates and co-expression of OPN. To demonstrate the effect of OPN on B cells, flow cytometry, ELISA and in vitro aggregation assays were conducted using the peripheral blood of healthy volunteers. Although OPN was expressed in MS brain tissue independent of B cell pathology, it was also highly expressed within B cell aggregates. In vitro studies demonstrated that OPN downregulated the co-stimulatory molecules CD80 and CD86 on B cells. OPN-treated B cells produced significantly lower amounts of IL-6. However, OPN-treated B cells also exhibited a higher tendency to form homotypic cell aggregates in vitro. Taken together, our data indicate a conflicting role of OPN in modulating B cell responses.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p$\le$ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.

Background: Multiple sclerosis (MS) is an immune‐mediated demyelinating disease of the central nervous system (CNS) with evidence of autoimmune attack also on the enteric nervous system (ENS). The role of different dietary antigens, including bovine milk proteins, in the exacerbation of MS symptoms has previously been discussed.Methods: In a mouse model of neuroinflammation, we characterized the extent of ENS pathology in animals that were immunized with different bovine milk antigens using electron microscopy, immunohistochemistry, molecular biology, and cell culture as key methods.Results: Our data demonstrate that immunization of mice with bovine milk casein resulted in ENS pathology, which is in line with our previous findings where casein‐immunized mice also exhibited demyelination in the CNS. Furthermore, development of ENS pathology was most likely due to a combination of cellular and humoral factors, as confirmed by our observation of CD3⁺ T cell infiltration in the tunica muscularis and binding of serum antibodies from casein‐immunized mice to glial cells in the myenteric plexus.Conclusion: The findings presented in this paper reflect that exposure to bovine casein can result in axolysis in the myenteric plexus possibly as a result of molecular mimicry and antibody cross‐reactivity between casein and antigen(s) expressed by the ENS.