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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model

  • Ahn, Ji-Su (Department of Life Science in Dentistry, School of Dentistry, Pusan National University) ;
  • Seo, Yoojin (Dental and Life Science Institute, Pusan National University) ;
  • Oh, Su-Jeong (Department of Life Science in Dentistry, School of Dentistry, Pusan National University) ;
  • Yang, Ji Won (Department of Life Science in Dentistry, School of Dentistry, Pusan National University) ;
  • Shin, Ye Young (Department of Life Science in Dentistry, School of Dentistry, Pusan National University) ;
  • Lee, Byung-Chul (Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Kang, Kyung-Sun (Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Sung, Eui-Suk (Department of Otorhinolaryngology, Head and Neck Surgery, Pusan National University Yangsan Hospital) ;
  • Lee, Byung-Joo (Department of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine) ;
  • Mohammadpour, Hemn (Department of Immunology, Roswell Park Comprehensive Cancer Center) ;
  • Hur, Jin (Department of Convergence Medicine, Pusan National University School of Medicine) ;
  • Shin, Tae-Hoon (Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health) ;
  • Kim, Hyung-Sik (Department of Life Science in Dentistry, School of Dentistry, Pusan National University)
  • Received : 2020.03.31
  • Accepted : 2020.04.30
  • Published : 2020.06.30
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Abstract

Inflammasomes are cytosolic, multiprotein complexes that act at the frontline of the immune responses by recognizing pathogen- or danger-associated molecular patterns or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects. In this study, we investigated the expression and functional regulation of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). hUCB-MSCs expressed inflammasome components that are necessary for its complex assembly. Interestingly, NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs.

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References

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