Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue.
The transcription factor T-bet was identified in CD4(+) T cells, and it controls interferon gamma production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432-3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet(-/-) mice is reduced. This is reproduced in adhesion studies using bone marrow-derived MCs (BMMCs) from T-bet(-/-) mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule-1 (MAdCAM-1) and vascular cell adhesion molecule-1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet(-/-) mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet(-/-) mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.
Alcaide
Pilar
P
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Jones
Tatiana G
TG
Lord
Graham M
GM
Glimcher
Laurie H
LH
Hallgren
Jenny
J
Arinobu
Yojiro
Y
Akashi
Koichi
K
Paterson
Alison M
AM
Gurish
Michael A
MA
Luscinskas
Francis W
FW
D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D003713:Dendritic Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007150:Immunohistochemistry; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins; D020545:Respiratory Mucosa / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000098815:T-bet Transcription Factor
D015815:Cell Adhesion Molecules; D017931:DNA Primers; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D019010:Vascular Cell Adhesion Molecule-1