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Inflammation

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Autotaxin-Lysophosphatidic Acid Axis Blockade Improves Inflammation by Regulating Th17 Cell Differentiation in DSS-Induced Chronic Colitis Mice

  • Ya-Lan Dong
  • Xue-Yun Duan
  • Yu-Jin Liu
  • Heng FanEmail author
  • Meng Xu
  • Qian-Yun Chen
  • Zhen Nan
  • Hui Wu
  • Shuang-Jiao Deng
Original Article
  • 109 Downloads

Abstract

Autotaxin-lysophosphatidic acid (ATX-LPA) axis is closely associated with several inflammation-related diseases. In the colonic mucosa of patients with chronic ulcerative colitis (UC), the expression of ATX and the percentage of Th17 cells are found to increase. However, it is unclear whether ATX-LPA axis affects the differentiation of Th17 cells in chronic UC. To investigate whether ATX-LPA axis contributes to Th17 cell differentiation, a mouse model of chronic UC was established by drinking water with DSS at intervals. ATX inhibitor was used as an intervention. The disease active index (DAI), colonic weight to length ratio, colon length, colon histopathology, and MAdCAM-1 were observed. Additionally, the expression of ATX, LPA receptor, CD34, IL-17A, IL-21, IL-6, ROR-γt, STAT3 in colonic tissue, and the percentage of Th17 cells in spleens and mesenteric lymph nodes (MLNs) were measured using different methods. ATX blockade was able to relieve symptoms and inflammatory response of DSS-induced chronic colitis. The DAI and colonic weight to length ratio were apparently decreased, while the colon length was increased. The pathological damage and colitis severity were lighter in the inhibitor group than that in the DSS group. Inhibiting ATX reduced the expression of ATX, LPA receptor, and CD34 and also decreased the percentages of Th17 cells in spleens and MLNs and the expressions of IL-17A and IL-21, as well as the factors in Th17 cell signaling pathway including IL-6, ROR-γt, and STAT3 in colonic tissue. ATX-LPA axis blockade could alleviate inflammation by suppressing Th17 cell differentiation in chronic UC.

KEY WORDS

ulcerative colitis (UC) autotaxin (ATX) lysophosphatidic acid (LPA) Th17 cell differentiation 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81573784 and 81774093).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ya-Lan Dong
    • 1
  • Xue-Yun Duan
    • 2
    • 3
  • Yu-Jin Liu
    • 1
  • Heng Fan
    • 1
    Email author
  • Meng Xu
    • 1
  • Qian-Yun Chen
    • 1
  • Zhen Nan
    • 1
  • Hui Wu
    • 1
  • Shuang-Jiao Deng
    • 1
  1. 1.Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Hubei Provincial Hospital of Traditional Chinese MedicineWuhanChina
  3. 3.Hubei Province Academy of Traditional Chinese MedicineWuhanChina

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