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Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation.
Blood 114, 1696-1706 (2009)
Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell-mediated autoimmune diseases. By dissecting Th1 cell-mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (Ecs). Adoptive transfer and mast cell knockin experiments into Kit(W)/Kit(W-v), TNF-/-, and TNFR1(-/-) mice showed that the signaling defect exclusively affects mast cell-EC interactions but not T cells or antigen-presenting cells. As a consequence, TNFR1(-/-) mice had strongly reduced mRNA and protein expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 during DTHR elicitation. In consequence, intravital fluorescence microscopy revealed up to 80% reduction of leukocyte rolling and firm adhesion in TNFR1(-/-) mice. As substitution of TNF-/- mice with TNF-producing mast cells fully restored DTHR in these mice, signaling of mast cell-derived TNF through TNFR1-expressing Ecs is essential for the recruitment of leukocytes into sites of inflammation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
tumor-necrosis-factor; contact hypersensitivity response; intercellular-adhesion molecule-1; versus-host-disease; factor-receptor; t-cells; p-selectin; mice deficient; ultraviolet-b; factor-alpha
Language
english
Publication Year
2009
HGF-reported in Year
0
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 114,
Issue: 8,
Pages: 1696-1706
Publisher
American Society of Hematology
Publishing Place
Washington
Reviewing status
Peer reviewed
Institute(s)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
Institute of Lung Health and Immunity (LHI)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30202 - Environmental Health
30202 - Environmental Health
Research field(s)
Immune Response and Infection
Lung Research
Lung Research
PSP Element(s)
G-501400-005
G-505000-001
G-505000-001
PubMed ID
19546478
Scopus ID
70349566472
Erfassungsdatum
2009-12-31