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

Y. Wang, S. Sedimbi, L. Löfbom, A. K. Singh, Steven A. Porcelli, S. L. Cardell

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 APC Min/+ 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 CD44 int, and PD-1 lo, 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 APC Min/+ mice, expression of T-helper (TH) 1-associated genes, such as IFN-β 3 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.

Original languageEnglish (US)
Pages (from-to)131-143
Number of pages13
JournalMucosal Immunology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2018

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Intestinal Polyps
Natural Killer T-Cells
Regulatory T-Lymphocytes
Immunity
Polyps
Phenotype
Interleukin-17
Zinc Fingers
Interleukin-10
Immunosuppression
Autoimmune Diseases
Colorectal Neoplasms
Neoplasms
Leukemia
Transcription Factors
Macrophages
Neoplasm Metastasis
Inflammation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells. / Wang, Y.; Sedimbi, S.; Löfbom, L.; Singh, A. K.; Porcelli, Steven A.; Cardell, S. L.

In: Mucosal Immunology, Vol. 11, No. 1, 01.01.2018, p. 131-143.

Research output: Contribution to journalArticle

Wang, Y. ; Sedimbi, S. ; Löfbom, L. ; Singh, A. K. ; Porcelli, Steven A. ; Cardell, S. L. / Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells. In: Mucosal Immunology. 2018 ; Vol. 11, No. 1. pp. 131-143.
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