PMID- 23839064
OWN - NLM
STAT- MEDLINE
DCOM- 20141017
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Print)
IS  - 1933-0219 (Linking)
VI  - 7
IP  - 2
DP  - 2014 Mar
TI  - IKKbeta in intestinal epithelial cells regulates allergen-specific IgA and allergic 
      inflammation at distant mucosal sites.
PG  - 257-67
LID - 10.1038/mi.2013.43 [doi]
AB  - Regulation of allergic responses by intestinal epithelial cells (IECs) remains 
      poorly understood. Using a model of oral allergen sensitization in the presence 
      of cholera toxin as adjuvant and mice with cell-specific deletion of inhibitor-kappaB 
      kinase (IKKbeta) in IECs (IKKbeta(DeltaIEC)), we addressed the contribution of IECs to 
      allergic sensitization to ingested antigens and allergic manifestations at 
      distant mucosal site of the airways. Cholera toxin induced higher 
      pro-inflammatory responses and altered the profile of the gut microbiota in 
      IKKbeta(DeltaIEC) mice. Antigen-specific immunoglobulin E (IgE) responses were unaltered 
      in IKKbeta(DeltaIEC) mice, but their IgA antibodies (Abs), T helper type 1 (Th1) and 
      Th17 responses were enhanced. Upon nasal antigen challenge, these mice developed 
      lower levels of allergic lung inflammation, which correlated with higher levels 
      of IgA Abs in the airways. The IKKbeta(DeltaIEC) mice also recruited a higher number of 
      gut-sensitized T cells in the airways after nasal antigen challenge and developed 
      airway hyper-responsiveness, which were suppressed by treatment with 
      anti-interleukin-17A. Fecal microbiota transplant during allergic sensitization 
      reduced Th17 responses in IKKbeta(DeltaIEC) mice, but did not affect IgA Ab responses. 
      In summary, we show that IKKbeta in IECs shapes the gut microbiota and immune 
      responses to ingested antigens and influences allergic responses in the airways 
      via regulation of IgA Ab responses.
FAU - Bonnegarde-Bernard, A
AU  - Bonnegarde-Bernard A
AD  - 1] Department of Veterinary Biosciences, The Ohio State University, Columbus, 
      Ohio, USA [2] Laboratory of Human Nutrition, Agro Paris Tech, Paris, France.
FAU - Jee, J
AU  - Jee J
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Fial, M J
AU  - Fial MJ
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Aeffner, F
AU  - Aeffner F
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Cormet-Boyaka, E
AU  - Cormet-Boyaka E
AD  - Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
FAU - Davis, I C
AU  - Davis IC
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Lin, M
AU  - Lin M
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Tome, D
AU  - Tome D
AD  - Laboratory of Human Nutrition, Agro Paris Tech, Paris, France.
FAU - Karin, M
AU  - Karin M
AD  - Department of Pharmacology, University of California, La Jolla, California, USA.
FAU - Sun, Y
AU  - Sun Y
AD  - Research and Testing Laboratory, Lubbock, Texas, USA.
FAU - Boyaka, P N
AU  - Boyaka PN
AD  - 1] Department of Veterinary Biosciences, The Ohio State University, Columbus, 
      Ohio, USA [2] Department of Internal Medicine, The Ohio State University, 
      Columbus, Ohio, USA.
LA  - eng
GR  - R01 AI043197/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130710
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Allergens)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Interleukin-17)
RN  - 9012-63-9 (Cholera Toxin)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Allergens/administration & dosage/*immunology
MH  - Animals
MH  - Antibody Specificity/immunology
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Cholera Toxin/immunology
MH  - Dysbiosis/immunology
MH  - Gene Deletion
MH  - I-kappa B Kinase/genetics/*metabolism
MH  - Immunity, Innate/genetics/immunology
MH  - Immunization
MH  - Immunoglobulin A/*immunology
MH  - Inflammation/*immunology/*metabolism
MH  - Interleukin-17/biosynthesis
MH  - Intestinal Mucosa/*immunology/*metabolism/pathology
MH  - Mice
MH  - Respiratory System/immunology/metabolism/pathology
MH  - Signal Transduction
PMC - PMC4053573
MID - NIHMS482892
EDAT- 2013/07/11 06:00
MHDA- 2014/10/18 06:00
PMCR- 2014/09/01
CRDT- 2013/07/11 06:00
PHST- 2012/12/22 00:00 [received]
PHST- 2013/05/13 00:00 [accepted]
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2014/10/18 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - S1933-0219(22)01044-3 [pii]
AID - 10.1038/mi.2013.43 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2014 Mar;7(2):257-67. doi: 10.1038/mi.2013.43. Epub 2013 Jul 10.