| The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in murine colitis model |
| Ji-Su Ahn1,# (Graduate student), Yoojin Seo2,# (Postdoctoral researcher), Su-Jeong Oh1 (Graduate student), Ji Won Yang1 (Graduate student), Ye Young Shin1 (Graduate student), Byung-Chul Lee3 (Postdoctoral researcher), Kyung-Sun Kang3 (Professor), Eui-Suk Sung4 (Professor), Byung-Joo Lee5 (Professor), Hemn Mohammadpour6 (Postdoctoral researcher), Jin Hur7 (Professor), Tae-Hoon Shin8 (Postdoctoral researcher), Hyung-Sik Kim1,2,* (Professor) |
1Department of Life Science in Dentistry, Pusan National University School of Dentistry,
2Dental and Life Science Institute, Pusan National University,
3Adult Stem Cell Research Center and Research Institute for Veterinary Science, Seoul National University,
4Department of Otorhinolaryngology, Pusan National University Yangsan Hospital,
5Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University Hospital,
6Department of Immunology, Roswell Park Comprehensive Cancer Center,
7Department of Convergence Medicine, Pusan National University School of Medicine,
8Translational Stem Cell Biology Branch, National Institutes of Health |
|
Abstract
Inflammasomes are cytosolic, multiprotein complexes which act at the frontline of the immune responses by recognizing pathogen or danger-associated molecular patterns of pathogens 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.
|
| Abstract, Accepted Manuscript(in press) [Submitted on March 31, 2020, Accepted on April 30, 2020] |
|