Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells

Abstract

CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen–free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110

Modulation of CD1d-restricted NKT cell responses by usingN-acyl variants of α-galactosylceramides

“…This more widespread presentation could lead to a more pronounced presentation of C20:2 by nonprofessional antigen-presenting cell types compared with KRN7000. Because many cell types express CD1d, including all hematopoietic lineages and various types of epithelia (44)(45)(46)(47)(48), presentation of C20:2 by nonprofessional antigen-presenting cells may explain the more rapid trans-activation of bystander cells observed with C20:2. An alternative hypothesis is that the endosomal loading requirements of KRN7000 result in its preferential localization into CD1d molecules contained in membrane lipid rafts, whereas the permissive loading properties of Fig.…”

Extracellular HSP110 skews macrophage polarization in colorectal cancer

“…Immunohistochemistry showed expression of HSP110 in epithelium from the small and large intestine. 30 As in vitro measurements showed low extracellular HSP110 concentrations in MSI-type CRC cell lines, it would be interesting to monitor variations in extracellular HSP110 amounts within body fluids as a new biomarker of disease characterization, or progression.…”

Come forth CD1d: Hsp110 in the regulation of intestinal epithelial CD1d expression

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