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

31 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 1 2007

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Mast Cells
Dendritic Cells
Mucous Membrane
Vascular Cell Adhesion Molecule-1
Bone Marrow
Trichinella spiralis
T-Lymphocytes
Adoptive Transfer
T-box transcription factor TBX21
Infection
Cell Adhesion
Interferons
Small Intestine
Intestines
Cell Differentiation
Leukocytes
Ligands
Lung

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. / Alcaide, Pilar; Jones, Tatiana G.; Lord, Graham M.; Glimcher, Laurie H.; Hallgren, Jenny; Arinobu, Yojiro; Akashi, Koichi; Paterson, Alison M.; Gurish, Michael A.; Luscinskas, Francis W.

In: Journal of Experimental Medicine, Vol. 204, No. 2, 01.02.2007, p. 431-439.

Research output: Contribution to journalArticle

Alcaide, P, Jones, TG, Lord, GM, Glimcher, LH, Hallgren, J, Arinobu, Y, Akashi, K, Paterson, AM, Gurish, MA & Luscinskas, FW 2007, 'Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue', Journal of Experimental Medicine, vol. 204, no. 2, pp. 431-439. https://doi.org/10.1084/jem.20060626
Alcaide, Pilar ; Jones, Tatiana G. ; Lord, Graham M. ; Glimcher, Laurie H. ; Hallgren, Jenny ; Arinobu, Yojiro ; Akashi, Koichi ; Paterson, Alison M. ; Gurish, Michael A. ; Luscinskas, Francis W. / Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 2. pp. 431-439.
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AU - Hallgren, Jenny

AU - Arinobu, Yojiro

AU - Akashi, Koichi

AU - Paterson, Alison M.

AU - Gurish, Michael A.

AU - Luscinskas, Francis W.

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