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https://doi.org/10.1038/s41467-018-03495-3
| Title: | Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis | Authors: | Mencarelli A. Khameneh H.J. Fric J. Vacca M. El Daker S. Janela B. Tang J.P. Nabti S. Balachander A. Lim T.S. Ginhoux F. Ricciardi-Castagnoli P. Mortellaro A. |
Keywords: | calcineurin CD11b antigen CD4 antigen cre recombinase dectin 1 glycoprotein p 15095 interleukin 10 interleukin 12 interleukin 12p40 interleukin 17 interleukin 2 interleukin 23 interleukin 6 major histocompatibility antigen class 2 myeloperoxidase transcription factor FOXP3 transcription factor NFAT transcription factor Nfat1 transcription factor Nfat2 transforming growth factor beta unclassified drug calcineurin glycoprotein p 15095 interleukin 2 antigen cation cell digestive system gene expression homeostasis immune system microorganism pathogen pathology protein rodent tolerance animal cell animal experiment animal model animal tissue Article bone marrow cell cell expansion cell population colitis controlled study disease association enteritis immune system immunological tolerance mouse nonhuman protein expression regulatory T lymphocyte signal transduction Th1 cell Th17 cell animal bone marrow cell C57BL mouse colitis female gene genetics homeostasis human immunology intestine knockout mouse male Mus Animals Calcineurin CD11c Antigen Colitis Female Genes, MHC Class II Homeostasis Humans Interleukin-2 Intestines Male Mice Mice, Inbred C57BL Mice, Knockout Myeloid Cells Th1 Cells Th17 Cells |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Mencarelli A., Khameneh H.J., Fric J., Vacca M., El Daker S., Janela B., Tang J.P., Nabti S., Balachander A., Lim T.S., Ginhoux F., Ricciardi-Castagnoli P., Mortellaro A. (2018). Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis. Nature Communications 9 (1) : 1102. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-03495-3 | Abstract: | The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-Antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chighMHCII+ cells (Cnb1 CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine. © 2018 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174235 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-018-03495-3 |
| Appears in Collections: | Elements Staff Publications |
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