Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue

Pilar Alcaide, Tatiana G. Jones, Graham M. Lord, Laurie H. Glimcher, Jenny Hallgren, Yojiro Arinobu, Koichi Akashi, Alison M. Paterson, Michael A. Gurish, Francis W. Luscinskas

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)431-439
Number of pages9
JournalJournal of Experimental Medicine
Volume204
Issue number2
DOIs
Publication statusPublished - Feb 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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