PMID- 28745029
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20211204
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Print)
IS  - 0105-4538 (Linking)
VI  - 73
IP  - 1
DP  - 2018 Jan
TI  - ADAM10 and Notch1 on murine dendritic cells control the development of type 2 
      immunity and IgE production.
PG  - 125-136
LID - 10.1111/all.13261 [doi]
AB  - BACKGROUND: Allergy and allergic asthma are significant health burdens in 
      developed countries and are increasing in prevalence. Dendritic cells (DCs) 
      initiate immune responses to common aeroallergens, and ADAM10 has been 
      demonstrated to be important for the development of adaptive responses. This 
      study's objective was to understand the role of ADAM10 on DCs in the development 
      of allergic and anaphylactic responses. METHODS: In this study, we used mouse 
      models of allergic airway inflammation (house dust mice and Alternaria alternata) 
      and OVA-induced models of active anaphylaxis to determine the DC-specific 
      function of ADAM10 and Notch signaling. To examine T(H) 1 and T(H) 17 immunity 
      infection with Anaplasma phagocytophilum and Citrobacter rodentium respectively, 
      were used. RESULTS: Mice, which have ADAM10 deleted from DCs, have dramatic 
      reductions in IgE production and do not develop significant T(H) 2 immune 
      responses. Further, ADAM10(DC)(-/-) mice are resistant to IgE-mediated 
      anaphylaxis. This response is selective for T(H) 2 immunity as T(H) 1 and T(H) 17 
      immunity is largely unaffected. Notch1, a known ADAM10 substrate, when knocked 
      out of DCs (Notch1(DC)(-/-) ) demonstrated a similar reduction in anaphylaxis and 
      IgE. Without ADAM10 and Notch1 signaling, DCs were unable to make cytokines that 
      stimulate T(H) 2 cells and cytokines. Anaphylaxis and allergic lung inflammation 
      were restored in ADAM10(DC)(-/-) with the overexpression of the 
      Notch1-intracellular domain, confirming the role of Notch signaling. CONCLUSIONS: 
      Targeting ADAM10 and Notch1 on DCs represent a novel strategy for modulating T(H) 
      2 immune responses and IgE production.
CI  - (c) 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
FAU - Damle, S R
AU  - Damle SR
AD  - Department of Microbiology and Immunology, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Martin, R K
AU  - Martin RK
AD  - Department of Microbiology and Immunology, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Cockburn, C L
AU  - Cockburn CL
AD  - Department of Microbiology and Immunology, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Lownik, J C
AU  - Lownik JC
AD  - Center for Clinical and Translational Research, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Carlyon, J A
AU  - Carlyon JA
AD  - Department of Microbiology and Immunology, Virginia Commonwealth University, 
      Richmond, VA, USA.
FAU - Smith, A D
AU  - Smith AD
AD  - United States Department of Agriculture, Diet, Genomics, and Immunology 
      Laboratory, Agricultural Research Service, Beltsville Human Nutrition Research 
      Center, Beltsville, MD, USA.
FAU - Conrad, D H
AU  - Conrad DH
AUID- ORCID: 0000-0002-4791-2694
AD  - Department of Microbiology and Immunology, Virginia Commonwealth University, 
      Richmond, VA, USA.
LA  - eng
GR  - K12 GM093857/GM/NIGMS NIH HHS/United States
GR  - P30 CA016059/CA/NCI NIH HHS/United States
GR  - P30 NS047463/NS/NINDS NIH HHS/United States
GR  - R01 AI018697/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170831
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-6)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.81 (Adam10 protein, mouse)
SB  - IM
MH  - ADAM10 Protein/genetics/*metabolism
MH  - Amyloid Precursor Protein Secretases/genetics/*metabolism
MH  - Anaphylaxis/immunology/metabolism
MH  - Animals
MH  - Biomarkers
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Hypersensitivity/immunology/metabolism
MH  - Immunoglobulin E/*immunology
MH  - Immunoglobulin G/blood/immunology
MH  - Interleukin-6/genetics/metabolism
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/genetics/metabolism
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Pyroglyphidae/immunology
MH  - Receptor, Notch1/genetics/*metabolism
MH  - Signal Transduction
MH  - Th1 Cells/immunology/metabolism
MH  - Th17 Cells/immunology/metabolism
MH  - Th2 Cells/immunology/metabolism
PMC - PMC5739941
MID - NIHMS894989
OTO - NOTNLM
OT  - IgE
OT  - animal models
OT  - asthma
OT  - dendritic cells
COIS- Conflicts of Interest Authors declare that they have no conflicts of interest.
EDAT- 2017/07/27 06:00
MHDA- 2018/07/10 06:00
PMCR- 2019/01/01
CRDT- 2017/07/27 06:00
PHST- 2017/07/20 00:00 [accepted]
PHST- 2017/07/27 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/07/27 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.1111/all.13261 [doi]
PST - ppublish
SO  - Allergy. 2018 Jan;73(1):125-136. doi: 10.1111/all.13261. Epub 2017 Aug 31.