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

Colgan, Sean P.; Pitman, Richard S.; Nagaishi, Takashi; Mizoguchi, Atsushi; Mizoguchi, Emiko; Mayer, Lloyd; Shao, Ling; Sartor, R. Balfour; Subjeck, John R.; Blumberg, Richard S.

doi:10.1172/jci17241

Cited by 16 publications

(30 citation statements)

References 34 publications

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“…This possibility is supported by other studies showing that the secretary form of gp96 can induce anti-tumour immunity (Baker-LePain et al, 2002). It has also been reported that HSP110 regulates expression of CD1d on intestinal epithelial cells (Colgan et al, 2003) suggesting another function of HSP110 as endogenous ''danger signal'' to facilitate induction of NK T cell-mediated anti-tumour immune responses.…”

Section: Article In Presssupporting

confidence: 55%

HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

et al. 2005

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Section: Article In Presssupporting

confidence: 55%

HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

et al. 2005

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“…Furthermore, consistent with regulation of CD1d expression by HSP110 (ref. 16), oxazolone colitis was associated with induction of CD1d expression in wild-type but not Mttp ΔIEC IECs (Extended Data Fig. 3c, right).…”

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confidence: 86%

“…HSP110, encoded by Hsph1 , exhibited decreased expression in Mttp ΔIEC mice (Fig. 2a), which was of interest given its known role in induction of epithelial CD1d expression 16 . In line with a potential MTP- and CD1d-dependent role of HSP110 in intestinal inflammation, HSP110 messenger RNA (Fig.…”

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confidence: 99%

Protective mucosal immunity mediated by epithelial CD1d and IL-10

Olszak

Neves

Dowds³

et al. 2014

Nature

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The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host1,2. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease3–8. As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref.9), decreased epithelial CD1d expression—as observed in inflammatory bowel disease10,11—may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1d elicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP)12,13, as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease.

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“…59 A notable characteristic of CD1d expression in the intestine is the increased expression with freshly isolated epithelial cells versus epithelial cell lines. 62 This suggests that factors are present in vivo that are uniquely capable of regulating CD1d expression. Recently, in testing this hypothesis, it was discovered that IEC expression of CD1d is induced by aqueous components from the normal human and murine milieu.…”

Section: The Intestinal Epithelial Cell a Novel Antigen-presenting Cmentioning

confidence: 99%

“…Recently, in testing this hypothesis, it was discovered that IEC expression of CD1d is induced by aqueous components from the normal human and murine milieu. 62 These factors were shown to be proteinaceous in character, and thus sensitive to heat denaturation, and to be of large molecular weight (> 100 kDa). 62 It was shown that these components exhibited activity within the intestinal lumen on multiple IEC lines and could be identified in the luminal milieu of germ-free mice, indicating a likely eukaryotic origin, rather than a prokaryotic one.…”

Section: The Intestinal Epithelial Cell a Novel Antigen-presenting Cmentioning

confidence: 99%

Natural Killer T Cells in Mucosal Homeostasis

Kaser

Nieuwenhuis

Strober

et al. 2004

Annals of the New York Academy of Sciences

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The mucosal-associated lymphoid tissues (MALT), including the gut-associated lymphoid tissues, are a tightly regulated environment. In fact, it might be stated that on the basis of studies from animal models of inflammatory bowel disease (IBD), the major means of peripheral regulation of immune responses in the intestine is not necessarily from processes such as deletion or anergy, but more likely from the controls imposed upon responses due to the activities of a variety of regulatory subsets of cells. One type of regulatory cellular subset that has recently gained attention is the subset of T cells that are associated with CD1d-restricted responses. Recently, CD1d-restricted T cells have been increasingly appreciated to play a significant role in mucosal tissues of the intestine and lung, for example. Insights from these studies have clearly elevated these cells to particular importance in the regulation of a variety of infectious and inflammatory conditions, such as those associated with idiopathic IBD. In this review, we focus on recent observations on the characteristics of CD1d-restricted pathways in mucosal compartments, after a brief introduction into the biology of CD1d and CD1d-restricted T cells.

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

Cited by 16 publications

References 34 publications

HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

Protective mucosal immunity mediated by epithelial CD1d and IL-10

Natural Killer T Cells in Mucosal Homeostasis

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