Figure 2.

The role of inflammasomes in multiple sclerosis (MS) and experimental autoimmune encephalitis (EAE). The autoimmune response for MS is believed to begin in the periphery. Activation of NLRP3 and NLRC4 inflammasome pathways in antigen-presenting cells (APC) enhance stimulation and differentiation of pathogenic CD4⁺ Th1/Th17 and CD8⁺ Tc1 subsets. On the other hand, NLRC3 activation in dendritic cells (DC) is protective against disease by inhibiting DC maturation. Secretion of IL-1β and IL-18 increase T cell expression of osteopontin (OPN), CCR2 (binding CCL7/8), and CXCR6 (binding CXCL16) to promote infiltration to the central nervous system (CNS). Upon activation and differentiation, CD4⁺ and CD8⁺ T cells, and B cells migrate to the CNS. In the CNS, peripheral DC, macrophages (MP), and monocytes (MO) further amplify inflammation. CNS resident cells such as microglia and astrocytes also promote inflammation. Lysophosphatidylcholine (LPC) activates NLRP3 and NLRC4, causing secretion of IL-1β and chemokines, leading to further inflammation and demyelination. NLRP9 expression is increased in microglia. NLRX1 and NLRP12 serve to down-regulate neuroinflammation and provide protection against disease as indicated by the red arrows. Reduction of NLRX1 and NLRP12 can lead to exacerbated disease states. Purinergic receptor (P2X7R). The figure was prepared using Biorender software licensed to the UNC Lineberger Comprehensive Cancer Center.