PMID- 19262503
OWN - NLM
STAT- MEDLINE
DCOM- 20090807
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Linking)
VI  - 2
IP  - 3
DP  - 2009 May
TI  - Cyclooxygenase-2 in mucosal DC mediates induction of regulatory T cells in the 
      intestine through suppression of IL-4.
PG  - 254-64
LID - 10.1038/mi.2009.2 [doi]
AB  - Oral intake of protein leads to tolerance through the induction of regulatory T 
      cells (Tr cells) in mesenteric lymph nodes (MLNs). Here we show that the 
      inhibition of cyclooxygenase-2 (COX-2) in vivo suppressed oral tolerance and was 
      associated with enhanced differentiation of interleukin (IL)-4-producing T cells 
      and reduced Foxp3(+) Tr-cell differentiation in MLN. As a result, the functional 
      suppressive capacity of these differentiated mucosal T cells was lost. IL-4 was 
      causally related to loss of tolerance as treatment of mice with anti-IL-4 
      antibodies during COX-2 inhibition restored tolerance. Dendritic cells (DCs) in 
      the MLN differentially expressed COX-2 and reductionist experiments revealed that 
      selective inhibition of the enzyme in these cells inhibited Foxp3(+) Tr-cell 
      differentiation in vitro. Importantly, the inhibition of COX-2 in MLN-DC caused 
      increased GATA-3 expression and enhanced IL-4 release by T cells, which was 
      directly related to impaired Tr-cell differentiation. These data provide crucial 
      insights into the mechanisms driving de novo Tr-cell induction and tolerance in 
      the intestine.
FAU - Broere, F
AU  - Broere F
AD  - Department of Molecular Cell Biology and Immunology, VU Medical Center, 
      Amsterdam, The Netherlands.
FAU - du Pre, M F
AU  - du Pre MF
FAU - van Berkel, L A
AU  - van Berkel LA
FAU - Garssen, J
AU  - Garssen J
FAU - Schmidt-Weber, C B
AU  - Schmidt-Weber CB
FAU - Lambrecht, B N
AU  - Lambrecht BN
FAU - Hendriks, R W
AU  - Hendriks RW
FAU - Nieuwenhuis, E E S
AU  - Nieuwenhuis EE
FAU - Kraal, G
AU  - Kraal G
FAU - Samsom, J N
AU  - Samsom JN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090304
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Sulfonamides)
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - 207137-56-2 (Interleukin-4)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/pharmacology
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/biosynthesis/*immunology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Cytokines/immunology
MH  - Dendritic Cells/drug effects/*enzymology/immunology
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - GATA3 Transcription Factor/genetics/metabolism
MH  - Immune Tolerance
MH  - Interleukin-4/antagonists & inhibitors/biosynthesis/*immunology
MH  - Intestinal Mucosa/cytology/*immunology/metabolism
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nitrobenzenes/pharmacology
MH  - Ovalbumin/immunology
MH  - Sulfonamides/pharmacology
MH  - T-Lymphocytes, Regulatory/cytology/*immunology
EDAT- 2009/03/06 09:00
MHDA- 2009/08/08 09:00
CRDT- 2009/03/06 09:00
PHST- 2009/03/06 09:00 [entrez]
PHST- 2009/03/06 09:00 [pubmed]
PHST- 2009/08/08 09:00 [medline]
AID - S1933-0219(22)01541-0 [pii]
AID - 10.1038/mi.2009.2 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2009 May;2(3):254-64. doi: 10.1038/mi.2009.2. Epub 2009 Mar 4.