title: Bile retinoids imprint intestinal CD103+ dendritic cells with the ability to generate gut-tropic T cells.
abstract: Small intestinal lamina propria (SI-LP) CD103(+) dendritic cells (DCs) are imprinted with an ability to metabolize vitamin A (retinol), a property underlying their enhanced capacity to induce the gut-homing receptors CC chemokine receptor-9 and α4β7 on responding T cells. In this study, we demonstrate that imprinting of CD103(+) DCs is itself critically dependent on vitamin A and occurs locally within the small intestine (SI). The major vitamin A metabolite retinoic acid (RA) induced retinol-metabolizing activity in DCs both in vitro and in vivo, suggesting a direct role for RA in this process. Consistent with this, SI-LP CD103(+) DCs constitutively received RA signals in vivo at significantly higher levels than did colonic CD103(+) DCs. Remarkably, SI CD103(+) DCs remained imprinted in mice depleted of dietary but not of systemic retinol. We found that bile contained high levels of retinol, induced RA receptor-dependent retinol-metabolizing activity in bone marrow-derived DCs, and imprinted these cells with the ability to generate gut-tropic T cells. Taken together, these results suggest a novel and unexpected role for bile in SI-LP CD103(+) DC imprinting.
authors.affiliation: Department of Experimental Medical Sciences, Immunology Section, Lund University, Lund, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Jaensson-Gyllenbäck
authors.forename: K
authors.initials: K
authors.lastname: Kotarsky
authors.forename: F
authors.initials: F
authors.lastname: Zapata
authors.forename: E K
authors.initials: EK
authors.lastname: Persson
authors.forename: T E
authors.initials: TE
authors.lastname: Gundersen
authors.forename: R
authors.initials: R
authors.lastname: Blomhoff
authors.forename: W W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001646:Bile / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004032:Diet; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR / Q000378:metabolism; D012176:Retinoids / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014801:Vitamin A / Q000032:analysis
chemical_list: D015703:Antigens, CD; C119309:CC chemokine receptor 9; D039001:Integrin alpha Chains; D054388:Receptors, CCR; D012176:Retinoids; C091367:alpha E integrins; D014801:Vitamin A