TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

Mesenchymal stem/stromal cells (MSCs) have an immunoregulatory capacity and have been used in different clinical protocols requiring control of the immune response. However, variable results have been obtained, mainly due to the effect of the microenvironment on the induction, increase, and maintenance of MSC immunoregulatory mechanisms. In addition, the importance of cell–cell contact for MSCs to efficiently modulate the immune response has recently been highlighted. Because these interactions would be difficult to achieve in the physiological context, the release of extracellular vesicles (EVs) and their participation as intermediaries of communication between MSCs and immune cells becomes relevant. Therefore, this article focuses on analyzing immunoregulatory mechanisms mediated by cell contact, highlighting the importance of intercellular adhesion molecule-1 (ICAM-1) and the participation of EVs. Moreover, the effects of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), the main cytokines involved in MSC activation, are examined. These cytokines, when used at the appropriate concentrations and times, would promote increases in the expression of immunoregulatory molecules in the cell and allow the acquisition of EVs enriched with these molecules. The establishment of certain in vitro activation guidelines will facilitate the design of conditioning protocols to obtain functional MSCs or EVs in different pathophysiological conditions.

The Role of NKT Cells in Glioblastoma

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

Preeclampsia is a multi-factorial and multi-genetic disorder that affects more than eight million mother and baby pairs each year. Currently, most of the attention to the pathogenesis of preeclampsia has been focused on placenta, but recent progresses suggest that excellent decidualization lays foundation for placentation and growth. Moreover, preeclampsia is associated with an imbalance in immunoregulatory mechanisms, however, how the immune regulatory system in the decidua affects preeclampsia is still unclear. In our study, after intersecting the genes of differentially expressed between preeclampsia and the control gotten by conventional expression profile analysis and the genes contained in the ligand receptor network, we found eight differentially expressed genes in a ligand-receptor relationship, and the eight genes have a characteristic: most of them participate in the interaction between decidual macrophages and other decidual immune cells. The results of single-cell sequencing of decidual cells further demonstrated that decidual macrophages affect the functions of other immune cells through export. As a result, abnormal gene expression affects the export function of decidual macrophages, which in turn affects the interaction of decidual macrophages with other immune cells, thereby destroying the original immune regulation mechanism, and ultimately leading to the occurrence of preeclampsia.

Changes in the spectrum of salivary cytokines in recurrent stomatitis in children

The concentration of the level of cytokines in saliva depends on the form of stomatitis, which is confirmed by the presence of a relationship between the concentrations of TNFα and IL-1β, and this relationship is direct and varies depending on the form of stomatitis, which indicates a violation of immunoregulatory mechanisms in chronic recurrent forms of stomatitis.