期刊
MUCOSAL IMMUNOLOGY
卷 11, 期 1, 页码 131-143出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2017.34
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资金
- Swedish Cancer Foundation
- Swedish Research Council
- Strategic Research Center for Mucosal Immunobiology and Vaccines (MIVAC)
- Assar Gabrielsson Foundation
- Adlerbertska Research Foundation
- Wilhelm and Martin Lundgren Science Foundation
- NIH R01 Grant [AI45889]
- Sahlgrenska Academy, University of Gothenburg
- Martin Lundgren Science Foundation
- PhD project grant
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI045889] Funding Source: NIH RePORTER
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKTcells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKTcells wereenriched for interleukin-10 (IL-10)-and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1.1(-) CD44(int), and PD-1(lo), and they were negative for the NKT cell transcription factor promyelocytic leukemia zinc-finger. The absence of iNKTcells was associated with a reduced frequency of regulatory T (Tregs) cells and lower expression levels of FoxP3 protein and transcript uniquely in the polyps, and a switch to an inflammatory macrophage phenotype. Moreover, in iNKT cell-deficient APC(Min/+) mice, expression of T-helper (TH) 1-associated genes, such as IFN-gamma and Nos2, was increased in polyps, concomitantly with elevated frequencies of conventional CD4(+) and CD8(+) T cells in this tissue. The results suggest that a population of regulatory iNKT cells locally promote intestinal polyp formation by enhancing Treg cells and immunosuppression of antitumor TH1 immunity.
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