Connecting liver and gut: murine liver sinusoidal endothelium induces gut tropism of CD4+ T cells via retinoic acid.
Hepatology
; 55(6): 1976-84, 2012 Jun.
Article
in En
| MEDLINE
| ID: mdl-22109893
ABSTRACT
UNLABELLED Gut-activated T cells migrating into the liver can cause extraintestinal manifestations of inflammatory bowel disease. T cells acquire a gut-homing phenotype dependent on retinoic acid (RA) provided by intestinal dendritic cells (DC). We investigated whether liver antigen-presenting cells can induce gut tropism supporting an enterohepatic lymphocyte circulation. Priming of CD4(+) T cells by liver sinusoidal endothelial cells (LSEC) supported migration into gut and gut-associated lymphoid tissue. As observed for T cells primed by intestinal DCs, this gut tropism depended on α(4) ß(7) integrin and CC chemokine receptor 9 (CCR9) expression by LSEC-primed CD4(+) T cells. The induction of gut-homing molecules was mediated by RA, a derivate of vitamin A that is stored in large amounts within the liver. LSECs expressed functional retinal dehydrogenases and could convert vitamin A to RA. Conversely, the lack of signaling via the RA receptor prevented the expression of α(4) ß(7) integrin and CCR9 on LSEC-primed CD4(+) T cells, consequently reducing their in vivo migration to the intestine. Other liver antigen-presenting cells failed to support high expression of α(4) ß(7) integrin on CD4(+) T cells, thus, the potential to induce gut homing is restricted to LSECs. CONCLUSION:
The capacity to promote gut tropism via vitamin A use is not unique for intestinal DCs but is also a feature of LSECs. Our data support the assumption that CD4(+) T cells can migrate from the liver to the gut as one branch of a postulated enterohepatic lymphocyte circulation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tretinoin
/
CD4-Positive T-Lymphocytes
/
Endothelial Cells
/
Intestines
/
Liver
Limits:
Animals
Language:
En
Journal:
Hepatology
Year:
2012
Type:
Article
Affiliation country:
Germany