期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 212, 期 1, 页码 15-22出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20130062
关键词
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资金
- European Research Council [206283]
- European Union's FP7 Cooperation Program (TARKINAID) [282095]
- Lendulet program of the Hungarian Academy of Sciences [LP2013-66]
- German Research Foundation (DFG) [DU1172/2, DU1172/3, 1468, 1394]
- Wellcome Trust International Senior Research Fellowship [087782]
- EAACI Exchange Research Fellowship
- [ASTF 56.00-2011]
- European Research Council (ERC) [206283] Funding Source: European Research Council (ERC)
Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases induced by contact allergens. Though numerous cellular and molecular players are known, the mechanism of chemical-induced sensitization remains poorly understood. Here, we identify neutrophils as crucial players in the sensitization phase of CHS. Genetic deficiency of neutrophils caused by myeloid-specific deletion of Mcl-1 or antibody-mediated depletion of neutrophils before sensitization abrogated the CHS response. Neutrophil deficiency reduced contact allergen-induced cytokine production, gelatinase release, and reactive oxygen species production in naive mice. Mast cell deficiency inhibited neutrophil accumulation at the site of sensitization. In turn, neutrophils were required for contact allergen-induced release of further neutrophil-attracting chemokines, migration of DCs to the draining lymph nodes, and priming of allergen-specific T cells. Lymph node cells from mice sensitized in the absence of neutrophils failed to transfer sensitization to naive recipients. Furthermore, no CHS response could be induced when neutrophils were depleted before elicitation or when normally sensitized lymph node cells were transferred to neutrophil-deficient recipients, indicating an additional role for neutrophils in the elicitation phase. Collectively, our data identify neutrophils to be critically involved in both the sensitization and elicitation phase of CHS.
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