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 language | English |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 294 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2007 |
| Externally published | Yes |
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Keywords
- CD4 T cells
- Chronic colitis
- Inflammatory bowel disease
- NKG2D
ASJC Scopus subject areas
- Gastroenterology
- Physiology
Cite this
Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitis. / Ito, Y.; Kanai, Takanori; Totsuka, T.; Okamoto, R.; Tsuchiya, K.; Nemoto, Y.; Yoshioka, A.; Tomita, T.; Nagaishi, T.; Sakamoto, N.; Sakanishi, T.; Okumura, K.; Yagita, H.; Watanabe, M.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 294, No. 1, 2007.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitis
AU - Ito, Y.
AU - Kanai, Takanori
AU - Totsuka, T.
AU - Okamoto, R.
AU - Tsuchiya, K.
AU - Nemoto, Y.
AU - Yoshioka, A.
AU - Tomita, T.
AU - Nagaishi, T.
AU - Sakamoto, N.
AU - Sakanishi, T.
AU - Okumura, K.
AU - Yagita, H.
AU - Watanabe, M.
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - CD4 T cells
KW - Chronic colitis
KW - Inflammatory bowel disease
KW - NKG2D
UR - http://www.scopus.com/inward/record.url?scp=38349134786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38349134786&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00286.2007
DO - 10.1152/ajpgi.00286.2007
M3 - Article
C2 - 17962357
AN - SCOPUS:38349134786
VL - 294
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 1
ER -