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Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient t...

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Autores principales: Hammerschmidt, Swantje I., Ahrendt, Manuela, Bode, Ulrike, Wahl, Benjamin, Kremmer, Elisabeth, Förster, Reinhold, Pabst, Oliver
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571923/
https://www.ncbi.nlm.nih.gov/pubmed/18852290
http://dx.doi.org/10.1084/jem.20080039
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author Hammerschmidt, Swantje I.
Ahrendt, Manuela
Bode, Ulrike
Wahl, Benjamin
Kremmer, Elisabeth
Förster, Reinhold
Pabst, Oliver
author_facet Hammerschmidt, Swantje I.
Ahrendt, Manuela
Bode, Ulrike
Wahl, Benjamin
Kremmer, Elisabeth
Förster, Reinhold
Pabst, Oliver
author_sort Hammerschmidt, Swantje I.
collection PubMed
description T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce α4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo.
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spelling pubmed-25719232009-04-27 Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo Hammerschmidt, Swantje I. Ahrendt, Manuela Bode, Ulrike Wahl, Benjamin Kremmer, Elisabeth Förster, Reinhold Pabst, Oliver J Exp Med Brief Definitive Reports T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce α4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo. The Rockefeller University Press 2008-10-27 /pmc/articles/PMC2571923/ /pubmed/18852290 http://dx.doi.org/10.1084/jem.20080039 Text en © 2008 Hammerschmidt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Reports
Hammerschmidt, Swantje I.
Ahrendt, Manuela
Bode, Ulrike
Wahl, Benjamin
Kremmer, Elisabeth
Förster, Reinhold
Pabst, Oliver
Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title_full Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title_fullStr Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title_full_unstemmed Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title_short Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
title_sort stromal mesenteric lymph node cells are essential for the generation of gut-homing t cells in vivo
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571923/
https://www.ncbi.nlm.nih.gov/pubmed/18852290
http://dx.doi.org/10.1084/jem.20080039
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