| First Author | Hosomi S | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 10 | Pages | 2985-2997 |
| PubMed ID | 28747426 | Mgi Jnum | J:249576 |
| Mgi Id | MGI:5922647 | Doi | 10.1084/jem.20162041 |
| Citation | Hosomi S, et al. (2017) Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation. J Exp Med 214(10):2985-2997 |
| abstractText | Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1(DeltaIEC) ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1(+) cells also significantly improved enteritis, whereas enteritis was not ameliorated in Recombinase activating gene 1(-/-);Xbp1(DeltaIEC) mice. These experiments reveal innate immune sensing of ER stress in IECs as an important mechanism of intestinal inflammation. |
