CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine.
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.
Wendland
Meike
M
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Czeloth
Niklas
N
Mach
Nicolas
N
Malissen
Bernard
B
Kremmer
Elisabeth
E
Pabst
Oliver
O
Förster
Reinhold
R
D019264:Adoptive Transfer; D000818:Animals; D002633:Chemotaxis / Q000276:immunology*; D002772:Cholera Toxin / Q000633:toxicity; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005759:Gastroenteritis / Q000139:chemically induced / Q000276:immunology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000276:immunology*
C119309:CC chemokine receptor 9; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D002772:Cholera Toxin