Work

Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice

Year: 2006

Type: article

Abstract: 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.

Source: Blood

DOI: 10.1182/blood-2006-09-046128

Authors: Susumu Nakae, Hajime Suto, Gerald J. Berry, Stephen J. Galli

Institutions: Stanford Medicine, Stanford University, Juntendo University

Language: English

Topic: Mast cells and histamine

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze