Fig. 7: Schematic diagram of mTORC2 signaling mediates γδ T cells migration into the fibrotic liver. | Cell Death & Disease

Fig. 7: Schematic diagram of mTORC2 signaling mediates γδ T cells migration into the fibrotic liver.

From: IL-1β-activated mTORC2 promotes accumulation of IFN-γ+ γδ T cells by upregulating CXCR3 to restrict hepatic fibrosis

Fig. 7: Schematic diagram of mTORC2 signaling mediates γδ T cells migration into the fibrotic liver.The alternative text for this image may have been generated using AI.

The hepatic immune microenvironment mediates chronic damage (e.g., alcohol and virus infection, etc.) induced hepatocyte injury, driving fibrogenesis by HSC activation. Resident hepatic macrophages, Kupffer cells (KC), are an important sensor of tissue injury. They become activated via pathogen-associated molecular patterns (PAMPs) from invading pathogens, by danger-associated molecular patterns (DAMPs) released from injured hepatocytes, proinflammatory cytokine (IL-1β) released from activated KC and infiltrating macrophage (IM) can initiate the γδ T cells CXCR3 expression by inducing mTORC2 activation, which in combination with the chemokines (CXCL9, CXCL10 and CXCL20, etc.) secreted by apoptotic hepatocytes and hepatic macrophages can stimulate the migration of γδ T cells into the fibrotic liver. Moreover, infiltrated γδ T cells exhibited potent cytotoxicity against activated aHSCs by Fas-FasL-dependent manner. Moreover, IFN-γ+ γδ T cells producing high levels of IFN-γ suppressed Th17 cell differentiation to ameliorate liver fibrosis. HSC hepatic stellate cells, KC Kupffer cell, IM infiltrating macrophage.

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