Mast cell-associated TNF promotes dendritic cell migration.
Mast cells represent a potential source of TNF, a mediator which can enhance dendritic cell (DC) migration. Although the importance of mast cell-associated TNF in regulating DC migration in vivo is not clear, mast cells and mast cell-derived TNF can contribute to the expression of certain models of contact hypersensitivity (CHS). We found that CHS to FITC was significantly impaired in mast cell-deficient Kit(W-sh/W-sh) or TNF(-/)(-) mice. The reduced expression of CHS in Kit(W-sh/W-sh) mice was fully repaired by local transfer of wild-type bone marrow-derived cultured mast cells (BMCMCs), but was only partially repaired by transfer of TNF(-/)(-) BMCMCs. Thus, mast cells, and mast cell-derived TNF, were required for optimal expression of CHS to FITC. We found that the migration of FITC-bearing skin DCs into draining lymph nodes (LNs) 24 h after epicutaneous administration of FITC in naive mice was significantly reduced in mast cell-deficient or TNF(-/)(-) mice, but levels of DC migration in these mutant mice increased to greater than wild-type levels by 48 h after FITC sensitization. Mast cell-deficient or TNF(-/)(-) mice also exhibited significantly reduced migration of airway DCs to local LNs at 24 h after intranasal challenge with FITC-OVA. Migration of FITC-bearing DCs to LNs draining the skin or airways 24 h after sensitization was repaired in Kit(W-sh/W-sh) mice which had been engrafted with wild-type but not TNF(-/)(-) BMCMCs. Our findings indicate that mast cell-associated TNF can contribute significantly to the initial stages of FITC-induced migration of cutaneous or airway DCs.
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Hajime
H
Suto
Susumu
S
Nakae
Maki
M
Kakurai
Jonathon D
JD
Sedgwick
Mindy
M
Tsai
Stephen J
SJ
Galli
D000281:Administration, Intranasal; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate