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Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities

Authors
 Changhon Lee  ;  Ravi Verma  ;  Seohyun Byun  ;  Eun-Ji Jeun  ;  Gi-Cheon Kim  ;  Suyoung Lee  ;  Hye-Ji Kang  ;  Chan Johng Kim  ;  Garima Sharma  ;  Abhishake Lahiri  ;  Sandip Paul  ;  Kwang Soon Kim  ;  Dong Soo Hwang  ;  Yoichiro Iwakura  ;  Immacolata Speciale  ;  Antonio Molinaro  ;  Cristina De Castro  ;  Dipayan Rudra  ;  Sin-Hyeog Im 7 
Citation
 NATURE COMMUNICATIONS, Vol.12(1) : 3611, 2021-06 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2021-06
MeSH
Animals ; CD4-Positive T-Lymphocytes ; Cell Differentiation / drug effects ; Colitis / immunology ; Colitis / pathology ; Cyclooxygenase 2 ; Dendritic Cells / immunology ; Encephalomyelitis, Autoimmune, Experimental ; Glucans ; Homeodomain Proteins / genetics ; Immunity ; Immunomodulation / drug effects* ; Immunomodulation / immunology* ; Lectins, C-Type ; Mannans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Polysaccharides / immunology* ; Polysaccharides / metabolism ; Polysaccharides / pharmacology ; Saccharomyces cerevisiae / genetics ; Saccharomyces cerevisiae / metabolism* ; T-Lymphocytes, Regulatory / drug effects ; T-Lymphocytes, Regulatory / immunology ; Th1 Cells ; Zymosan ; beta-Glucans / immunology* ; beta-Glucans / metabolism ; beta-Glucans / pharmacology
Abstract
Yeast is an integral part of mammalian microbiome, and like commensal bacteria, has the potential of being harnessed to influence immunity in clinical settings. However, functional specificities of yeast-derived immunoregulatory molecules remain elusive. Here we find that while under steady state, β-1,3-glucan-containing polysaccharides potentiate pro-inflammatory properties, a relatively less abundant class of cell surface polysaccharides, dubbed mannan/β-1,6-glucan-containing polysaccharides (MGCP), is capable of exerting potent anti-inflammatory effects to the immune system. MGCP, in contrast to previously identified microbial cell surface polysaccharides, through a Dectin1-Cox2 signaling axis in dendritic cells, facilitates regulatory T (Treg) cell induction from naïve T cells. Furthermore, through a TLR2-dependent mechanism, it restrains Th1 differentiation of effector T cells by suppressing IFN-γ expression. As a result, administration of MGCP display robust suppressive capacity towards experimental inflammatory disease models of colitis and experimental autoimmune encephalomyelitis (EAE) in mice, thereby highlighting its potential therapeutic utility against clinically relevant autoimmune diseases.
DOI
10.1038/s41467-021-23929-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gi-Cheon(김기천)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190890
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