CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine

doi:10.1073/pnas.0609180104

CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine

*Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
^†Oncology Division, Geneva University Hospital, 1211 Geneva, Switzerland;
^‡Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, U631, Centre National de la Recherche Scientifique, UMR6102, 13288 Marseille Cedex 9, France; and
^§GSF National Research Center for Environment and Health, Institute of Molecular Immunology, 81377 Munich, Germany

Edited by Dan R. Littman, New York University Medical Center, New York, NY, and approved February 23, 2007 (received for review October 17, 2006)

Abstract

Small intestine plasmacytoid dendritic cells (pDC) are poorly characterized. Here, we demonstrate that intestinal pDC show the characteristic plasma cell-like morphology, and are recognized by antibodies against B220, Ly6c, 120G8, and PDCA-1, markers that are typically expressed by pDC. Furthermore, intestinal pDC carry high levels of CCR9 and are largely absent in the intestine, but not in lung, liver, or secondary lymphoid organs of CCR9-deficient animals. Competitive adoptive transfers reveal that CCR9-deficient pDC are impaired in homing to the small intestine after i.v. transfer. In a model of cholera toxin-induced gut inflammation, pDC are recruited to the intestine in WT but not CCR9-deficient animals. Furthermore, after oral application of a Toll-like receptor (TLR) 7/8 ligand, myeloid DC of the lamina propria are rapidly mobilized in WT but not in CCR9-deficient animals. Mobilization of myeloid DC can be completely rescued by adoptively transferred WT pDC to CCR9-deficient mice before oral challenge. Together, our data reveal an essential role for CCR9 in the homing of pDC to the intestine under homeostatic and inflammatory conditions and demonstrate an important role for intestinal pDC for the rapid mobilization of lamina propria DC.

Footnotes

^¶To whom correspondence should be addressed at:
Institute of Immunology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany.
E-mail: foerster.reinhold{at}mh-hannover.de
Author contributions: O.P. and R.F. contributed equally to this work; O.P. and R.F. designed research; M.W. and N.C. performed research; N.M., B.M., and E.K. contributed new reagents/analytic tools; M.W. and N.C. analyzed data; and R.F. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0609180104/DC1.
Abbreviations:

DC,

dendritic cell;

mDC,

myeloid DC;

pDC,

plasmacytoid DC;

TLR,

Toll-like receptor;

Flt3L,

fms-like tyrosine kinase3 ligand;

LN,

lymph node;

LP,

lamina propria;

IE,

intraepithelial;

PP,

Peyer's patches;

BM,

bone marrow;

CFSE,

carboxyfluorescein diacetate-succinimidyl ester;

TAMRA,

carboxytetramethylrhodamine;

CT,

cholera toxin.