Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells.
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.
Colgan
Sean P
SP
Center for Experimental Therapeutics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Pitman
Richard S
RS
Nagaishi
Takashi
T
Mizoguchi
Atsushi
A
Mizoguchi
Emiko
E
Mayer
Lloyd F
LF
Shao
Ling
L
Sartor
R Balfour
RB
Subjeck
John R
JR
Blumberg
Richard S
RS
D000595:Amino Acid Sequence; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008969:Molecular Sequence Data
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C097205:HSPH1 protein, human