PMID- 20881191
OWN - NLM
STAT- MEDLINE
DCOM- 20101112
LR  - 20101021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 9
DP  - 2010 Nov 1
TI  - Efficient induction of CCR9 on T cells requires coactivation of retinoic acid 
      receptors and retinoid X receptors (RXRs): exaggerated T Cell homing to the 
      intestine by RXR activation with organotins.
PG  - 5289-99
LID - 10.4049/jimmunol.1000101 [doi]
AB  - The active vitamin A metabolite retinoic acid (RA) imprints gut-homing 
      specificity on lymphocytes upon activation by inducing the expression of alpha4beta7 
      integrin and CCR9. RA receptor (RAR) activation is essential for their 
      expression, whereas retinoid X receptor (RXR) activation is not essential for 
      alpha4beta7 expression. However, it remains unclear whether RXR activation affects the 
      RA-dependent CCR9 expression on T cells and their gut homing. The major 
      physiological RA, all-trans-RA, binds to RAR but not to RXR at physiological 
      concentrations. Cell-surface CCR9 expression was often induced on a limited 
      population of murine naive CD4(+) T cells by all-trans-RA or the RAR agonist Am80 
      alone upon CD3/CD28-mediated activation in vitro, but it was markedly enhanced by 
      adding the RXR agonist PA024 or the RXR-binding environmental chemicals 
      tributyltin and triphenyltin. Accordingly, CD4(+) T cells treated with the 
      combination of all-trans-RA and tributyltin migrated into the small intestine 
      upon adoptive transfer much more efficiently than did those treated with 
      all-trans-RA alone. Furthermore, naive TCR transgenic CD4(+) T cells transferred 
      into wild-type recipients migrated into the small intestinal lamina propria 
      following i.p. injection of Ag, and the migration was enhanced by i.p. injection 
      of PA024. We also show that PA024 markedly enhanced the all-trans-RA-induced CCR9 
      expression on naturally occurring naive-like regulatory T cells upon activation, 
      resulting in the expression of high levels of alpha4beta7, CCR9, and Foxp3. These 
      results suggest that RXR activation enhances the RAR-dependent expression of CCR9 
      on T cells and their homing capacity to the small intestine.
FAU - Takeuchi, Hajime
AU  - Takeuchi H
AD  - Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 
      Kagawa, Japan.
FAU - Yokota, Aya
AU  - Yokota A
FAU - Ohoka, Yoshiharu
AU  - Ohoka Y
FAU - Kagechika, Hiroyuki
AU  - Kagechika H
FAU - Kato, Chieko
AU  - Kato C
FAU - Song, Si-Young
AU  - Song SY
FAU - Iwata, Makoto
AU  - Iwata M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100929
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CC chemokine receptor 9)
RN  - 0 (Organotin Compounds)
RN  - 0 (Receptors, CCR)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Animals
MH  - Cell Separation
MH  - Chemotaxis, Leukocyte/drug effects/*immunology
MH  - Flow Cytometry
MH  - Intestines/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Organotin Compounds/*pharmacology
MH  - Receptors, CCR/*biosynthesis/immunology
MH  - Receptors, Retinoic Acid/immunology/*metabolism
MH  - Retinoid X Receptors/immunology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Regulatory/drug effects/immunology/*metabolism
EDAT- 2010/10/01 06:00
MHDA- 2010/11/13 06:00
CRDT- 2010/10/01 06:00
PHST- 2010/10/01 06:00 [entrez]
PHST- 2010/10/01 06:00 [pubmed]
PHST- 2010/11/13 06:00 [medline]
AID - jimmunol.1000101 [pii]
AID - 10.4049/jimmunol.1000101 [doi]
PST - ppublish
SO  - J Immunol. 2010 Nov 1;185(9):5289-99. doi: 10.4049/jimmunol.1000101. Epub 2010 
      Sep 29.