CD1d, a nonclassical MHC class I–like molecule, is prominently expressed on intestinal epithelial cells and is thought to function in the regulation of intestinal intraepithelial lymphocyte activity. Hsp110, an abundant heat shock protein present in essentially all mammalian tissues, has now been shown to upregulate CD1d expression in colonic tissue culture cell lines. Might this abundant chaperone serve an autocrine function in the regulation of CD1d expression?
Christopher V. Nicchitta
Hypothetical model for an Hsp110 function in IEC CD1d expression. (I) In this speculative model, Hsp110 release from IECs occurs during the physiological process of epithelial renewal and contributes, directly or indirectly, to the regulation of CD1d expression. In the case of normal (physiological) epithelial cell renewal, Hsp110 is released, whereupon it serves to signal normal (physiological) levels of CD1d expression. In this scenario, CD1d-directed NK T cell activation leads to the induction of IL-4 and IL-10 release and suppression of inflammatory responses. (II) In the case of accelerated (pathological) IEC death, Hsp110 release may be elevated, leading to enhanced levels of CD1d expression and perhaps alterations in the identity or relative quantity of CD1d ligands. In this scenario, NK T cells would be activated to yield release of the proinflammatory cytokines IFN-γ and TNF-α, thereby promoting the induction of inflammatory disease. TCR, T cell receptor.