Abstract
Abstract Invariant natural killer T (iNKT) cells are a subset of glycolipid reactive T cells, implicated in the protection against microbial pathogens and immune regulation. While the pathways leading to iNKT cell activation in the context of infectious diseases have been uncovered, much less is known how iNKT cells become activated in the context of chronic inflammatory diseases. Here, we unveil a novel mode of iNKT cell activation which occurs during chronic TNF driven inflammation through generation of inflammatory dendritic cells. This in turn, leads to a spontaneous activation of iNKT cells by promoting CD1d mediated presentation of endogenous glycolipids. This mode of activation is capable of attenuating combined Crohn's like ileitis and joint inflammation occurring in TNFΔARE mice, and thus may represent a natural counter regulatory mechanism to dampen TNF driven inflammation.
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