Figure 2.

Schematic representation of adaptive immune mechanisms in MS and AD. In CNS, CD4⁺ T cells producing the pro-inflammatory mediators IFN-γ-and IL-17 promote microglial activation, upregulating the expression of CD40, MHC-II, CD80, and CD86 on the surface and favoring neuroinflammation. CD8⁺ T cells producing IFN-γ bind neurons expressing MHC-I, triggering neuronal damage and boosting neuroinflammation. Dysregulated T_reg cells fail to suppress effector T cell functions (red crosses), thus sustaining the neuroinflammatory environment. In the intestine, the microbiome and its metabolites influence the polarization and activation of T cells. Bacteroides fragilis promotes the expansion of T_reg cells, the amino acids phenylalanine and isoleucine induce the differentiation of Th1 cells, and segmented filamentous bacteria trigger Th17 cell polarization. Vascular endothelial cells express the LFA-1 and VLA-4 counter-ligands (ICAM-1 and VCAM-1) guiding the transmigration of peripherally activated T cells from the circulation to the CNS.