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¹ Center for Excellence in Vascular Biology, Department of Pathology and ² Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
³ Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, 02115
⁴ Department of Medicine and ⁵ Department of Pathology, Harvard Medical School, Boston, MA, 02115
⁶ Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Francis W. Luscinskas: fluscinskas{at}rics.bwh.harvard.edu

The transcription factor T-bet was identified in CD4⁺ T cells, and it controls interferon 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.

Abbreviations used: BaP, basophil progenitor; BMDC, BM-derived DC; BMCP, basophil MC progenitor; BMMC, BM-derived MC; CXCL and CXCR, CXC chemokine ligand and receptor, respectively; GMP, granulocyte monocyte progenitor; KC, keratinocyte-derived chemokine; MAdCAM-1, mucosal addresin cellular adhesion molecule–1; MC, mast cell; MCp, MC progenitor(s); MNC, mononuclear cell; PMC, peritoneal MC; SCF, stem cell factor; SDF-1, stromal cell–derived factor 1; SIBR, sublethally irradiated BM reconstituted; Tc1, T cytotoxic type 1; VCAM-1, vascular cell adhesion molecule–1.

P. Alcaide, T.G. Jones, and G.M. Lord contributed equally to this work.

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