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Related Experiment Videos

Mast cell-associated TNF promotes dendritic cell migration.

Hajime Suto1, Susumu Nakae, Maki Kakurai

  • 1Department of Pathology, Stanford University School of Medicine, CA 94305, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|March 21, 2006
PubMed
Summary

Mast cells and their derived TNF are crucial for the initial migration of dendritic cells (DCs) in contact hypersensitivity (CHS) responses. This study clarifies their essential role in immune cell trafficking and allergic reactions.

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Area of Science:

  • Immunology
  • Dermatology
  • Allergy Research

Background:

  • Mast cells are implicated as a source of TNF, a cytokine that can influence dendritic cell (DC) migration.
  • The precise role of mast cell-derived TNF in regulating DC migration in vivo, particularly in contact hypersensitivity (CHS), remains incompletely understood.

Purpose of the Study:

  • To investigate the necessity of mast cells and mast cell-derived TNF in the development of FITC-induced CHS.
  • To determine the impact of mast cells and TNF on the migration of DCs to lymph nodes in both skin and airway models.

Main Methods:

  • Utilized mast cell-deficient (Kit(W-sh/W-sh)) and TNF-deficient (TNF(-/-)) mice to assess CHS responses to FITC.
  • Employed bone marrow-derived cultured mast cells (BMCMCs) for reconstitution experiments in deficient mice.

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  • Quantified the migration of FITC-bearing DCs to draining lymph nodes (LNs) at 24 and 48 hours post-sensitization via skin or airway challenge.

    • Main Results:

    • CHS responses to FITC were significantly impaired in mast cell-deficient and TNF-deficient mice.
    • Transfer of wild-type BMCMCs fully restored CHS in deficient mice, while TNF-deficient BMCMCs only partially restored it.
    • Reduced migration of FITC-bearing DCs to LNs at 24 hours was observed in deficient mice, with levels increasing by 48 hours.
    • This early DC migration defect was specifically repaired by wild-type BMCMCs, not TNF-deficient ones, highlighting TNF's role.

    Conclusions:

    • Mast cells and mast cell-derived TNF are essential for the optimal expression of FITC-induced CHS.
    • Mast cell-associated TNF significantly contributes to the early-stage migration of cutaneous and airway DCs following sensitization.
    • These findings elucidate a key mechanism in immune cell trafficking during allergic contact dermatitis and airway inflammation.