Bile retinoids imprint intestinal CD103 + dendritic cells with the ability to generate gut-tropic T cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : E Jaensson-Gyllenb ن ck 1 , 4 , K Kotarsky 1 , 4 , F Zapata 1 , EK Persson 1 , TE Gundersen 2 , R Blomhoff 2 , 3 and WW Agace 1
- چاپ و سال / کشور: 2011
Description
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 4 7 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.
1 Department of Experimental Medical Sciences, Immunology Section, Lund University , Lund , Sweden . 2 Vitas AS, Oslo Innovation Park , Oslo , Norway . 3 Institute of Basic Medical Sciences, University of Oslo , Oslo , Norway . 4 These authors contributed equally to this work . Correspondence: W Agace ( William.Agace@med.lu.se ) Received 26 November 2010; accepted 16 December 2010; advance online publication 2 February 2011. doi: 10.1038/mi.2010.91
