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Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells.

Journal article
Authors Ying Wang
S Sedimbi
Linda Löfbom
Avadhesh Kumar Singh
S A Porcelli
Susanna Cardell
Published in Mucosal immunology
Volume 11
Issue 1
Pages 131-143
ISSN 1935-3456
Publication year 2017
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 131-143
Language en
Links dx.doi.org/10.1038/mi.2017.34
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Tumour immunology

Abstract

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 iNKT cells markedly decreased the total number of intestinal polyps in APCMin/+ mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4+, NK1.1- CD44int, and PD-1lo, and they were negative for the NKT cell transcription factor promyelocytic leukemia zinc-finger. The absence of iNKT cells 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 APCMin/+ mice, expression of T-helper (TH) 1-associated genes, such as IFN-γ 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.Mucosal Immunology advance online publication 12 April 2017; doi:10.1038/mi.2017.34.

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