| First Author | Malik A | Year | 2023 |
| Journal | Nature | Volume | 623 |
| Issue | 7989 | Pages | 1044-1052 |
| PubMed ID | 37993709 | Mgi Jnum | J:349216 |
| Mgi Id | MGI:7647084 | Doi | 10.1038/s41586-023-06721-1 |
| Citation | Malik A, et al. (2023) Epithelial IFNgamma signalling and compartmentalized antigen presentation orchestrate gut immunity. Nature 623(7989):1044-1052 |
| abstractText | All nucleated cells express major histocompatibility complex I and interferon-gamma (IFNgamma) receptor(1), but an epithelial cell-specific function of IFNgamma signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNgamma, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages. By contrast, antigen presentation by the tissue macrophages alongside inflammasome-associated interleukin-1alpha and interleukin-1beta production promotes a pathogenic transformation of CD4(+) T cells into granulocyte-macrophage colony-stimulating-factor (GM-CSF)-producing T cells in vivo, which promotes colitis and colorectal cancer. Taken together, our study unravels critical checkpoints requiring IFNgamma sensing and antigen presentation by epithelial cells that control the development of pathogenic CD4(+) T cell responses in vivo. |
