A unique population of IFNγ-producing innate lymphoid cells promotes Campylobacter-induced colitis

Autor: Wayne T Muraoka, Qingqing Xia, Sydney Halperin, Ekaterina Koroleva, Alexei Tumanov
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:208.1-208.1
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.208.1
Popis: Inflammatory bowel diseases (IBD) are thought to arise from an overly aggressive immune response to the intestinal microbiota. Campylobacter jejuni is a human enteric pathogen that is a major cause of gastroenteritis worldwide. C. jejuni infection also increases the risk of developing IBD-like sequelae. Prior studies showed IL-10 deficient mice develop fulminant colitis when infected by C. jejuni. However, the roles of adaptive and innate immune cells in promoting colitis remain unresolved. Here, we show that T cells are not necessary for C. jejuni-induced colitis. In vivo depletion of Thy1+ cells or neutralization of IFNγ in T cell deficient mice significantly ameliorated C. jejuni-induced colitis, indicating a pathogenic role for IFNγ-producing innate lymphoid cells (ILC1s). In mice, ILC1s are currently identified as NK1.1+NKp46+ cells and prior studies reported that depleting NK1.1+ cells ameliorated ILC1-driven colitis. Unexpectedly, despite effective depletion of NK1.1+ cells in mice lacking T cells, this treatment did not impact IFNγ production or colon pathology after C. jejuni infection. Phenotyping analysis revealed IFNγ-producing ILCs (Thy1+Lin−Tbet+Eomes−GnzA−RORγtlow/−) that accumulated in the colon during C. jejuni-induced colitis did not express NK1.1 or NKp46. Further, mice deficient for the transcription factor RORγt possessed markedly fewer NK1.1−NKp46− ILC1s in the intestine and exhibited reduced severity of C. jejuni-induced colitis. Based on the lack of NK and natural cytotoxicity receptors (NCR) and in accord with the current ILC nomenclature, we propose the tentative designation of NCR−ILC1. Together, these results identified a unique population of ILC1s that promote colitis.
Databáze: OpenAIRE
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