Oncotarget

Research Papers:

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis

Fan Wang, Pai-Lan Peng, Xue Lin, Ying Chang, Jing Liu, Rui Zhou, Jia-Yan Nie, Wei-Guo Dong, Qiu Zhao and Jin Li _

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Oncotarget. 2017; 8:98945-98952. https://doi.org/10.18632/oncotarget.22132

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Abstract

Fan Wang1,3,*, Pai-Lan Peng2,4,*, Xue Lin5, Ying Chang1,3, Jing Liu1,3, Rui Zhou1,3, Jia-Yan Nie1,3, Wei-Guo Dong2, Qiu Zhao1,3 and Jin Li1,3

1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

2Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China

3Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China

4Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000 China

5Department of Critical Care Medicine, The People’s Hospital of Huangshan, Huangshan 245000 China

*These authors have contributed equally to this work

Correspondence to:

Jin Li, email: [email protected]

Wei-Guo Dong, email: [email protected]

Qiu Zhao, email: [email protected]

Keywords: intestinal lamina propria; NKG2D; natural killer cells; ulcerative colitis

Received: June 16, 2017    Accepted: August 26, 2017    Published: October 30, 2017

ABSTRACT

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn’s colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.


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