The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model

被引:24
作者
Ahn, Ji-Su [1 ]
Seo, Yoojin [2 ]
Oh, Su-Jeong [1 ]
Yang, Ji Won [1 ]
Shin, Ye Young [1 ]
Lee, Kyung-Jae [3 ,4 ]
Kang, Kyung-Sun [3 ,4 ]
Sung, Eui-Suk [5 ]
Lee, Byung-Joo [6 ]
Mohammadpour, Hemn [7 ]
Hur, Jin [8 ]
Shin, Tae-Hoon [9 ]
Kim, Hyung-Sik [1 ,2 ]
机构
[1] Pusan Natl Univ, Sch Dent, Dept Life Sci Dent, Yangsan 50612, South Korea
[2] Pusan Natl Univ, Dent & Life Sci Inst, Yangsan 50612, South Korea
[3] Seoul Natl Univ, Coll Vet Med, Adult Stem Cell Res Ctr, Seoul 08826, South Korea
[4] Seoul Natl Univ, Coll Vet Med, Res Inst Vet Sci, Seoul 08826, South Korea
[5] Pusan Natl Univ, Dept Otorhinolaryngol Head & Neck Surg, Yangsan Hosp, Yangsan 50612, South Korea
[6] Pusan Natl Univ, Pusan Natl Univ Hosp, Biomed Res Inst, Dept Otorhinolaryngol Head & Neck Surg,Sch Med, Busan 49241, South Korea
[7] Roswell Park Comprehens Canc Ctr, Dept Immunol, Buffalo, NY 14203 USA
[8] Pusan Natl Univ, Dept Convergence Med, Sch Med, Yangsan 50612, South Korea
[9] NHLBI, Translat Stem Cell Biol Branch, NIH, Bethesda, MD 20892 USA
基金
新加坡国家研究基金会;
关键词
Colitis; Immunomodulation; Inflammasome; Mesenchymal stem cell; NLRP3; TOLL-LIKE RECEPTORS; MARROW STROMAL CELLS; IMMUNOSUPPRESSIVE PROPERTIES; RECOGNITION; PROLIFERATION; SUPPRESSION; INHIBIT; PROTEIN; DAMAGE;
D O I
10.5483/BMBRep.2020.53.6.065
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Inflammasomes are cytosolic, multiprotein complexes that ad 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.
引用
收藏
页码:329 / 334
页数:6
相关论文
共 41 条
[1]
Pathogen recognition and innate immunity [J].
Akira, S ;
Uematsu, S ;
Takeuchi, O .
CELL, 2006, 124 (04) :783-801
[2]
Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis [J].
Augello, Andrea ;
Tasso, Roberta ;
Negrini, Simone Maria ;
Cancedda, Ranieri ;
Pennesi, Giuseppina .
ARTHRITIS AND RHEUMATISM, 2007, 56 (04) :1175-1186
[3]
Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression [J].
Bauernfeind, Franz G. ;
Horvath, Gabor ;
Stutz, Andrea ;
Alnemri, Emad S. ;
MacDonald, Kelly ;
Speert, David ;
Fernandes-Alnemri, Teresa ;
Wu, Jianghong ;
Monks, Brian G. ;
Fitzgerald, Katherine A. ;
Hornung, Veit ;
Latz, Eicke .
JOURNAL OF IMMUNOLOGY, 2009, 183 (02) :787-791
[4]
Genetic analysis of resistance to viral infection [J].
Beutler, Bruce ;
Eidenschenk, Celine ;
Crozat, Karine ;
Imler, Jean-Luc ;
Takeuchi, Osamu ;
Hoffmann, Jules A. ;
Akira, Shizuo .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (10) :753-766
[5]
Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness [J].
Beyth, S ;
Borovsky, Z ;
Mevorach, D ;
Liebergall, M ;
Gazit, Z ;
Aslan, H ;
Galun, E ;
Rachmilewitz, J .
BLOOD, 2005, 105 (05) :2214-2219
[6]
The Inflammasomes and Autoinflammatory Syndromes [J].
Broderick, Lori ;
De Nardo, Dominic ;
Franklin, Bernardo S. ;
Hoffman, Hal M. ;
Latz, Eicke .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 10, 2015, 10 :395-424
[7]
The receptor NLRP3 is a transcriptional regulator of TH2 differentiation [J].
Bruchard, Melanie ;
Rebe, Cedric ;
Derangere, Valentin ;
Togbe, Dieudonnee ;
Ryffel, Bernhard ;
Boidot, Romain ;
Humblin, Etienne ;
Hamman, Arlette ;
Chalmin, Fanny ;
Berger, Helene ;
Chevriaux, Angelique ;
Limagne, Emeric ;
Apetoh, Lionel ;
Vegran, Frederique ;
Ghiringhelli, Francois .
NATURE IMMUNOLOGY, 2015, 16 (08) :859-+
[8]
Role of toll-like receptors on human adipose-derived stromal cells [J].
Cho, Hyun Hwa ;
Bae, Yong Chan ;
Jung, Jin Sup .
STEM CELLS, 2006, 24 (12) :2744-2752
[9]
Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses [J].
Gonzalez, Manuel A. ;
Gonzalez-Rey, Elena ;
Rico, Laura ;
Buescher, Dirk ;
Delgado, Mario .
GASTROENTEROLOGY, 2009, 136 (03) :978-989
[10]
The immune response of Drosophila [J].
Hoffmann, JA .
NATURE, 2003, 426 (6962) :33-38