PMID- 33205040
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240404
IS  - 2590-0064 (Electronic)
IS  - 2590-0064 (Linking)
VI  - 8
DP  - 2020 Sep
TI  - Developing immune-regulatory materials using immobilized monosaccharides with 
      immune-instructive properties.
PG  - 100080
LID - 10.1016/j.mtbio.2020.100080 [doi]
LID - 100080
AB  - New strategies for immune modulation have shown real promise in regenerative 
      medicine as well as the fight against autoimmune diseases, allergies, and cancer. 
      Dendritic cells (DCs) are gatekeepers of the immune system and their ability in 
      shaping the adaptive immune responses makes DCs ideal targets for immune 
      modulation. Carbohydrates are abundant in different biological systems and are 
      known to modulate DC phenotype and function. However, how simple monosaccharides 
      instruct DC function is less well understood. In this study, we used a 
      combinatorial array of immobilized monosaccharides to investigate how they 
      modulate DC phenotype and function and crucially the impact of such changes on 
      downstream adaptive immune responses. Our data show that a selection of 
      monosaccharides significantly suppress lipopolysaccharide-induced DC activation 
      as evidenced by a reduction in CD40 expression, IL-12 production, and indoleamine 
      2,3-dioxygenase activity, while inducing a significant increase in IL-10 
      production. These changes are indicative of the induction of an anti-inflammatory 
      or regulatory phenotype in DCs, which was further confirmed in DC-T cell 
      co-cultures where DCs cultured on the 'regulatory' monosaccharide-coated surfaces 
      were shown to induce naive T cell polarization toward regulatory phenotype. Our 
      data also highlighted a selection of monosaccharides that are able to promote 
      mixed Treg and Th17 cell differentiation, a T cell phenotype expected to be 
      highly immune suppressive. These data show the potential immunomodulatory effects 
      of immobilized monosaccharides in priming DCs and skewing T cell differentiation 
      toward an immune-regulatory phenotype. The ability to fine-tune immune responses 
      using these simple carbohydrate combinations (e.g. as coatings for existing 
      materials) can be utilized as novel tools for immune modulation with potential 
      applications in regenerative medicine, implantable medical devices, and wound 
      healing where reduction of inflammatory responses and maintaining immune 
      homeostasis are desirable.
CI  - (c) 2020 The Authors.
FAU - Alobaid, M A
AU  - Alobaid MA
AD  - Immunology & Immuno-Bioengineering, School of Life Sciences, Faculty of Medicine 
      and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Richards, S-J
AU  - Richards SJ
AD  - Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United 
      Kingdom.
FAU - Alexander, M R
AU  - Alexander MR
AD  - School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Gibson, M I
AU  - Gibson MI
AD  - Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United 
      Kingdom.
AD  - Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom.
FAU - Ghaemmaghami, A M
AU  - Ghaemmaghami AM
AD  - Immunology & Immuno-Bioengineering, School of Life Sciences, Faculty of Medicine 
      and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
AD  - Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90024, USA.
LA  - eng
PT  - Journal Article
DEP - 20200930
PL  - England
TA  - Mater Today Bio
JT  - Materials today. Bio
JID - 101757228
PMC - PMC7649522
OTO - NOTNLM
OT  - (Gal1), 100% 1-amino-1-deoxy-beta-d-galactose
OT  - (Gal1-Gal2), 50% 1-amino-1-deoxy-beta-d-galactose + 50% 
      2-amino-2-deoxy-beta-d-galactose
OT  - (Gal2), 100% 2-amino-2-deoxy-beta-d-galactose
OT  - (Gal2-Man1), 90% 2-amino-2-deoxy-beta-d-galactose + 10% 1-amino-1-deoxy-beta-d-mannose
OT  - (Gal2-Man2), 2-amino-2-deoxy-beta-d-galactose + 10% 2-amino-2-deoxy-beta-d-mannose
OT  - (Man1-Man2), 40% 1-amino-1-deoxy-beta-d-mannose + 60% 2-amino-2-deoxy-beta-d-mannose
OT  - CLR, C-type lectin receptor
OT  - Carbohydrates
OT  - DC-SIGN, Dendritic cell-specific intercellular adhesion molecule 3-grabbing 
      nonintegrin
OT  - DCs, Dendritic cells
OT  - Dendritic cells
OT  - FBS, Fetal bovine serum
OT  - Fucose
OT  - Galactose
OT  - IDO, Indoleamine 2,3-dioxygenase
OT  - Immune modulation
OT  - Immune-instructive materials
OT  - LPS, Lipopolysaccharide
OT  - MFI, Median fluorescence intensity
OT  - MR, Mannose receptor
OT  - MT, 1-methyl-DL-tryptophan
OT  - Mannose
OT  - PRR, Pattern recognition receptor
OT  - Polymers
OT  - T cells
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this article.
EDAT- 2020/11/19 06:00
MHDA- 2020/11/19 06:01
PMCR- 2020/09/30
CRDT- 2020/11/18 06:01
PHST- 2020/07/02 00:00 [received]
PHST- 2020/09/17 00:00 [revised]
PHST- 2020/09/21 00:00 [accepted]
PHST- 2020/11/18 06:01 [entrez]
PHST- 2020/11/19 06:00 [pubmed]
PHST- 2020/11/19 06:01 [medline]
PHST- 2020/09/30 00:00 [pmc-release]
AID - S2590-0064(20)30040-5 [pii]
AID - 100080 [pii]
AID - 10.1016/j.mtbio.2020.100080 [doi]
PST - epublish
SO  - Mater Today Bio. 2020 Sep 30;8:100080. doi: 10.1016/j.mtbio.2020.100080. 
      eCollection 2020 Sep.