Mast cells (MCs) are immune cells that play a critical role in both innate and adaptive immunity. In neuroinflammation, MCs are involved in the production of pro-inflammatory cytokines such as TNF and IL-33, which contribute to the pathogenesis of brain diseases. TNF is stored in MC granules and can be released upon activation, leading to the production of other inflammatory cytokines and chemokines. IL-33, a member of the IL-1 family, is also produced by MCs and activates immune responses through the ST2L/IL1-RAcP receptor complex. Both TNF and IL-33 are involved in the activation of microglia and other immune cells, contributing to neuroinflammation. MCs can be activated by various stimuli, including IgE binding to FcεRI and antigens, leading to the release of inflammatory mediators. The activation of MCs can lead to the production of pro-inflammatory cytokines and chemokines, which mediate inflammatory responses in the central nervous system (CNS). TNF and IL-33 have dual roles in neuroinflammation, as they can both promote and regulate immune responses. The inhibition of TNF and IL-33 may represent a new therapeutic approach for neuroinflammatory diseases. MCs also interact with other immune cells, such as T cells and macrophages, to modulate immune responses in the CNS. The study highlights the importance of MCs in neuroinflammation and suggests that targeting TNF and IL-33 could be a promising strategy for treating neuroinflammatory disorders.Mast cells (MCs) are immune cells that play a critical role in both innate and adaptive immunity. In neuroinflammation, MCs are involved in the production of pro-inflammatory cytokines such as TNF and IL-33, which contribute to the pathogenesis of brain diseases. TNF is stored in MC granules and can be released upon activation, leading to the production of other inflammatory cytokines and chemokines. IL-33, a member of the IL-1 family, is also produced by MCs and activates immune responses through the ST2L/IL1-RAcP receptor complex. Both TNF and IL-33 are involved in the activation of microglia and other immune cells, contributing to neuroinflammation. MCs can be activated by various stimuli, including IgE binding to FcεRI and antigens, leading to the release of inflammatory mediators. The activation of MCs can lead to the production of pro-inflammatory cytokines and chemokines, which mediate inflammatory responses in the central nervous system (CNS). TNF and IL-33 have dual roles in neuroinflammation, as they can both promote and regulate immune responses. The inhibition of TNF and IL-33 may represent a new therapeutic approach for neuroinflammatory diseases. MCs also interact with other immune cells, such as T cells and macrophages, to modulate immune responses in the CNS. The study highlights the importance of MCs in neuroinflammation and suggests that targeting TNF and IL-33 could be a promising strategy for treating neuroinflammatory disorders.