Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice.
Both mast cells and IL-17 can contribute to host defense and pathology in part by orchestrating neutrophil recruitment, but the possible role of mast cells in IL-17-induced inflammation remains to be defined. We found that mast cells and IL-17, but neither IFN-gamma nor FcRgamma signaling, contributed significantly to the antigen (Ag)-dependent airway neutrophilia elicited in ovalbumin-specific T-cell receptor (TCR)-expressing C57BL/6-OTII mice, and that IFN-gamma significantly suppressed IL-17-dependent airway neutrophilia in this setting. IL-18, IL-1beta, and TNF each contributed significantly to the development of Ag- and T helper 17 (Th17 cell)-mediated airway neutrophilia. Moreover, IL-17 enhanced mast cell TNF production in vitro, and mast cell-associated TNF contributed significantly to Ag- and Th17 cell-mediated airway neutrophilia in vivo. By contrast, we detected no significant role for the candidate mediators histamine, PGD(2), LTB(4), CXCL10, or IL-16, each of which can be produced by mast cells and other cell types, in the neutrophil infiltration elicited in this model. These findings establish that mast cells and mast cell-derived TNF can significantly enhance, by FcRgamma-independent mechanisms, the Ag- and Th17 cell-dependent development of a neutrophil-rich inflammatory response at a site of Ag challenge.
Nakae
Susumu
S
Department of Pathology L-235, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. nakae@stanford.edu
Suto
Hajime
H
Berry
Gerald J
GJ
Galli
Stephen J
SJ
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000633:toxicity; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000941:Antigens; D018836:Inflammation Mediators; D020381:Interleukin-17; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin