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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3640-3648.
Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-09-046128.
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CHEMOKINES, CYTOKINES, AND INTERLEUKINS
Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice
Susumu Nakae1,
Hajime Suto1,2,
Gerald J. Berry1, and
Stephen J. Galli1
1 Department of Pathology, Stanford University School of Medicine, Stanford, CA;
2 Atopy Research Center, Juntendo University, Tokyo, Japan
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- nor FcR 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- significantly suppressed IL-17–dependent airway neutrophilia in this setting. IL-18, IL-1ß, 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, PGD2, LTB4, 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 FcR-independent mechanisms, the Ag- and Th17 cell–dependent development of a neutrophil-rich inflammatory response at a site of Ag challenge.
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