Dysregulation of CD1d-restricted type II natural killer T cells leads to spontaneous development of colitis in mice

Chiamin Liao, Michael I. Zimmer, Sharmila Shanmuganad, Hontsen Yu, Susanna L. Cardell, Chyungru Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Background & Aims: CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis. Methods: To investigate whether dysregulation of type II NKT cells, caused by increased expression of CD1d, can contribute to colitis, we generated transgenic mice that express high levels of CD1d and a TCR from an autoreactive, type II NKT cell (CD1dTg/24αβTg mice). Results: CD1dTg/24αβTg mice had reduced numbers of 24αβ T cells compared with 24αβTg mice, indicating that negative selection increases among type II NKT cells engaged by abundant self-antigen. The residual 24αβ T cells in CD1dTg/24αβTg mice had an altered surface phenotype and acquired a cytokine profile distinct from that of equivalent cells in 24αβTg mice. Interestingly, CD1dTg/24αβTg mice spontaneously developed colitis; adoptive transfer experiments confirmed that type II NKT cells that develop in the context of increased CD1d expression are pathogenic. Conclusions: Aberrant type II NKT cell responses directly contribute to intestinal inflammation in mice, indicating the importance of CD1d expression levels in the development and regulation of type II NKT cells.

Original languageEnglish (US)
Pages (from-to)326-334.e2
JournalGastroenterology
Volume142
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Crohn's Disease
  • IBD
  • Immune Regulation
  • T-Cell Development

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Dysregulation of CD1d-restricted type II natural killer T cells leads to spontaneous development of colitis in mice'. Together they form a unique fingerprint.

  • Cite this