PMID- 26703454
OWN - NLM
STAT- MEDLINE
DCOM- 20170615
LR  - 20211204
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 137
IP  - 6
DP  - 2016 Jun
TI  - The mannose receptor negatively modulates the Toll-like receptor 4-aryl 
      hydrocarbon receptor-indoleamine 2,3-dioxygenase axis in dendritic cells 
      affecting T helper cell polarization.
PG  - 1841-1851.e2
LID - S0091-6749(15)01642-5 [pii]
LID - 10.1016/j.jaci.2015.10.033 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are key players in the induction and 
      re-elicitation of TH2 responses to allergens. We have previously shown that 
      different C-type lectin receptors on DCs play a major role in allergen 
      recognition and uptake. In particular, mannose receptor (MR), through modulation 
      of Toll-like receptor (TLR) 4 signaling, can regulate indoleamine 2,3-dioxygenase 
      (IDO) activity, favoring TH2 responses. Interestingly, the aryl hydrocarbon 
      receptor (AhR), a ligand-dependent transcription factor with an emerging role in 
      immune modulation, has been implicated in IDO activation in response to TLR 
      stimulation. OBJECTIVE: Here we investigated how allergens and lectins modulate 
      the TLR4-AhR-IDO axis in human monocyte-derived DCs. METHODS: Using a combination 
      of genomics, proteomics, and immunologic studies, we investigated the role of MR 
      and AhR in IDO regulation and its effect on T helper cell differentiation. 
      RESULTS: We have demonstrated that LPS induces both IDO isoforms (IDO1 and IDO2) 
      in DCs, with partial involvement of AhR. Additionally, we found that, like 
      mannan, different airborne allergens can effectively downregulate TLR4-induced 
      IDO1 and IDO2 expression, most likely through binding to the MR. Mannose-based 
      ligands were also able to downregulate IL-12p70 production by DCs, affecting T 
      helper cell polarization. Interestingly, AhR and some components of the 
      noncanonical nuclear factor kappaB pathway were shown to be downregulated after MR 
      engagement, which could explain the regulatory effects of MR on IDO expression. 
      CONCLUSION: Our work demonstrates a key role for MR in the modulation of the 
      TLR4-AhR-IDO axis, which has a significant effect on DC behavior and the 
      development of immune responses against allergens.
CI  - Copyright (c) 2015 American Academy of Allergy, Asthma & Immunology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Salazar, Fabian
AU  - Salazar F
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom.
FAU - Hall, Laurence
AU  - Hall L
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom.
FAU - Negm, Ola H
AU  - Negm OH
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom; Medical 
      Microbiology and Immunology Department, Mansoura University, Mansoura, Egypt.
FAU - Awuah, Dennis
AU  - Awuah D
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom.
FAU - Tighe, Patrick J
AU  - Tighe PJ
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom.
FAU - Shakib, Farouk
AU  - Shakib F
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom.
FAU - Ghaemmaghami, Amir M
AU  - Ghaemmaghami AM
AD  - Division of Immunology, School of Life Sciences, Faculty of Medicine and Health 
      Sciences, University of Nottingham, Nottingham, United Kingdom. Electronic 
      address: amg@nottingham.ac.uk.
LA  - eng
PT  - Journal Article
DEP - 20151217
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Allergens)
RN  - 0 (Cytokines)
RN  - 0 (IDO1 protein, human)
RN  - 0 (IDO2 protein, human)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Ligands)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Allergens/immunology
MH  - Cluster Analysis
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*metabolism
MH  - Interleukin-12/biosynthesis
MH  - Lectins, C-Type/*metabolism
MH  - Ligands
MH  - Lymphocyte Activation/immunology
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/*metabolism
MH  - Monocytes/cytology/immunology/metabolism
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Receptors, Cell Surface/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Helper-Inducer/*immunology/*metabolism
MH  - Toll-Like Receptor 4/agonists/metabolism
OTO - NOTNLM
OT  - C-type lectin receptor
OT  - Dendritic cells
OT  - T(H)2
OT  - Toll-like receptor 4
OT  - allergy
OT  - aryl-hydrocarbon receptor
OT  - indoleamine 2,3-dioxygenase
OT  - mannose receptor
OT  - nuclear factor kappaB
EDAT- 2015/12/26 06:00
MHDA- 2017/06/16 06:00
CRDT- 2015/12/26 06:00
PHST- 2015/06/09 00:00 [received]
PHST- 2015/10/09 00:00 [revised]
PHST- 2015/10/27 00:00 [accepted]
PHST- 2015/12/26 06:00 [entrez]
PHST- 2015/12/26 06:00 [pubmed]
PHST- 2017/06/16 06:00 [medline]
AID - S0091-6749(15)01642-5 [pii]
AID - 10.1016/j.jaci.2015.10.033 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2016 Jun;137(6):1841-1851.e2. doi: 
      10.1016/j.jaci.2015.10.033. Epub 2015 Dec 17.