期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 204, 期 2, 页码 431-439出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20060626
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资金
- MRC [G108/380] Funding Source: UKRI
- Medical Research Council [G108/380] Funding Source: Medline
- NCI NIH HHS [R01 CA112663, CA112663] Funding Source: Medline
- NHLBI NIH HHS [HL56985, P01 HL036028, R01 HL053993, P01 HL036110, HL36028, HL53993, P50 HL056985, HL 036110] Funding Source: Medline
- NIAID NIH HHS [AI56296, P01 AI031599, U19 AI031599, P01 AI056296, AI 031599] Funding Source: Medline
- Medical Research Council [G0400503B, G108/380] Funding Source: researchfish
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.
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