Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitis

Y. Ito, T. Kanai, T. Totsuka, R. Okamoto, K. Tsuchiya, Y. Nemoto, A. Yoshioka, T. Tomita, T. Nagaishi, N. Sakamoto, T. Sakanishi, K. Okumura, H. Yagita, M. Watanabe

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Abstract

It has been recently demonstrated that NKG2D is an activating costimulatory receptor on natural killer (NK) cells, natural killer T (NKT) cells, activated CD8+ T cells, and γδ T cells, which respond to cellular stress, such as inflammation, transformation, and infection. Here we show that intestinal inflammation in colitic SCID mice induced by adoptive transfer of CD4+CD45RBhigh T cells is characterized by significant increase of CD4+NKG2D+ T cells and constitutive expression of NKG2D ligands, such as H60, Mult-1, and Rae-1, by lamina propria CD11c + dendritic cells. Furthermore, treatment with nondepleting and neutralizing anti-NKG2D MAb after transfer of CD4+CD45RB high T cells into SCID mice significantly suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of IFN-γ by lamina propria CD4+ T cells. These findings demonstrate that NKG2D signaling pathway is critically involved in CD4 + T cell-mediated disease progression and suggest a new therapeutic target for inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)G199-G207
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number1
DOIs
Publication statusPublished - 2007 Dec 1

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Keywords

  • CD4 T cells
  • Chronic colitis
  • Inflammatory bowel disease
  • NKG2D

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Ito, Y., Kanai, T., Totsuka, T., Okamoto, R., Tsuchiya, K., Nemoto, Y., Yoshioka, A., Tomita, T., Nagaishi, T., Sakamoto, N., Sakanishi, T., Okumura, K., Yagita, H., & Watanabe, M. (2007). Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 294(1), G199-G207. https://doi.org/10.1152/ajpgi.00286.2007