PMID- 20118218
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20220316
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 44
IP  - 3
DP  - 2011 Mar
TI  - Allergy risk is mediated by dendritic cells with congenital epigenetic changes.
PG  - 285-92
LID - 10.1165/rcmb.2009-0400OC [doi]
AB  - One factor predisposing toward allergic responses is a maternal history of 
      allergy. In a mouse model of maternal transmission of asthma risk, offspring of 
      asthmatic, but not normal, mothers show increased allergic susceptibility, 
      recreating epidemiologic observations in humans. Dendritic cells (DCs) capture 
      and process antigens, and can skew immune responses toward a pro-allergic T 
      helper 2 phenotype. Genome-wide analysis shows that neonates of allergic mothers 
      are born with substantial changes in DNA methylation in their splenic CD11c(+) 
      DCs, findings observed without any contact with allergens. We demonstrate that 
      these DCs from allergen-naive neonates born to asthmatic mothers, but not DCs 
      from offspring of normal mothers, confer increased allergic susceptibility to 
      multiple allergens when adoptively transferred into normal recipient mice, 
      manifesting as increased airway responsiveness and allergic inflammation. Other 
      immune splenocytes, including macrophages and CD4+ T cells, did not transfer the 
      effect. The "asthma-susceptible" DCs also show enhanced allergen-presentation 
      activity in vitro. Our findings suggest that maternal allergy results in an 
      altered epigenetic profile in neonatal DCs that is independent of encounters with 
      allergens and is linked to pro-allergic function.
FAU - Fedulov, Alexey V
AU  - Fedulov AV
AD  - Department of Environmental Health, Harvard School of Public Health, Boston, MA 
      02115, USA. afedulov@hsph.harvard.edu
FAU - Kobzik, Lester
AU  - Kobzik L
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100129
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (CD11c Antigen)
RN  - 0 (Cytokines)
SB  - IM
CIN - Am J Respir Cell Mol Biol. 2011 Dec;45(6):1272; author reply 1272-3. PMID: 
      22140201
MH  - Animals
MH  - CD11c Antigen/biosynthesis
MH  - Cytokines/metabolism
MH  - *DNA Methylation
MH  - Dendritic Cells/*cytology
MH  - Disease Models, Animal
MH  - *Epigenesis, Genetic
MH  - Female
MH  - Flow Cytometry
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Hypersensitivity/*genetics/*immunology
MH  - Macrophages/cytology
MH  - Maternal Exposure
MH  - Mice
MH  - Pregnancy
MH  - Risk
MH  - Spleen/cytology/immunology
PMC - PMC3095930
EDAT- 2010/02/02 06:00
MHDA- 2011/04/28 06:00
PMCR- 2012/03/01
CRDT- 2010/02/02 06:00
PHST- 2010/02/02 06:00 [entrez]
PHST- 2010/02/02 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - 2009-0400OC [pii]
AID - ajrcmb443285 [pii]
AID - 10.1165/rcmb.2009-0400OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2011 Mar;44(3):285-92. doi: 10.1165/rcmb.2009-0400OC. 
      Epub 2010 Jan 29.