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

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 Castro, Dipayan Rudra () and Sin-Hyeog Im ()
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Changhon Lee: Pohang University of Science and Technology (POSTECH)
Ravi Verma: Pohang University of Science and Technology (POSTECH)
Seohyun Byun: Pohang University of Science and Technology (POSTECH)
Eun-Ji Jeun: Pohang University of Science and Technology (POSTECH)
Gi-Cheon Kim: Yonsei University College of Medicine
Suyoung Lee: Pohang University of Science and Technology (POSTECH)
Hye-Ji Kang: Handong Global University
Chan Johng Kim: Pohang University of Science and Technology (POSTECH)
Garima Sharma: Pohang University of Science and Technology (POSTECH)
Abhishake Lahiri: CSIR-Indian Institute of Chemical Biology
Sandip Paul: CSIR-Indian Institute of Chemical Biology
Kwang Soon Kim: Pohang University of Science and Technology (POSTECH)
Dong Soo Hwang: Pohang University of Science and Technology (POSTECH)
Yoichiro Iwakura: Tokyo University of Science
Immacolata Speciale: University of Napoli
Antonio Molinaro: University of Naples Federico II
Cristina Castro: University of Napoli
Dipayan Rudra: Pohang University of Science and Technology (POSTECH)
Sin-Hyeog Im: Pohang University of Science and Technology (POSTECH)

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23929-9

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