Fig. 3: Key immune signals along the gut–immune–brain axis.
From: Beyond the gut: decoding the gut–immune–brain axis in health and disease
Gut-mediated immune signaling regulates brain function. In the intestine, Th17 cells are induced by SFB and IL-17A during early brain development and are linked to ASD-associated behaviors. During inflammatory conditions such as EAE, IFN-γ-producing NK cells are recruited to the brain in a gut microbiome-dependent manner, where they promote anti-inflammatory astrocyte responses. Dysbiosis induces the production of proinflammatory cytokines that disrupt BBB integrity. Conversely, butyrate promotes IL-22 production by ILCs and CD4⁺ T cells, enhancing BBB stability via direct effects on endothelial cells. CNS-resident T cells secrete cytokines to modulate brain function: IFN-γ regulates neuronal activity, IL-4 regulates microglial synaptic pruning, and IL-4 and IL-13 aid in inhibitory synapse formation. Peripheral cytokines, including IL-2, which drives Treg expansion, and IL-33, which suppresses proinflammatory Th17/Th1 responses, also influence CNS-resident immune cells. The role of the gut microbiota in these processes remains to be elucidated
