期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 136, 期 3, 页码 747-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2015.03.011
关键词
Asthma; receptor for advanced glycation end-products; IL-33; group 2 innate lymphoid cells
资金
- National Institutes of Health (NIH) [5R21HL095495-02, 1T32HL094295-01A2, 5T32HL094295-0304, 1F30ES024045-01, AI048927, HL113956]
Background: Single nucleotide polymorphisms in the human gene for the receptor for advanced glycation end-products (RAGE) are associated with an increased incidence of asthma. RAGE is highly expressed in the lung and has been reported to play a vital role in the pathogenesis of murine models of asthma/allergic airway inflammation (AAI) by promoting expression of the type 2 cytokines IL-5 and IL-13. IL-5 and IL-13 are prominently secreted by group 2 innate lymphoid cells (ILC2s), which are stimulated by the proallergic cytokine IL-33. Objective: We sought to test the hypothesis that pulmonaryRAGE is necessary for allergen-induced ILC2 accumulation in the lung. Methods: AAI was induced in wild-type and RAGE knockout mice by using IL-33, house dust mite extract, or Alternaria alternata extract. RAGE's lung-specific role in type 2 responses was explored with bone marrow chimeras and induction of gastrointestinal type 2 immune responses. Results: RAGE was found to drive AAI by promoting IL-33 expression in response to allergen and by coordinating the inflammatory response downstream of IL-33. Absence of RAGE impedes pulmonary accumulation of ILC2s in models of AAI. Bone marrow chimera studies suggest that pulmonary parenchymal, but not hematopoietic, RAGE has a central role in promoting AAI. In contrast to the lung, the absence of RAGE does not affect IL-33-induced ILC2 influx in the spleen, type 2 cytokine production in the peritoneum, or mucus hypersecretion in the gastrointestinal tract. Conclusions: For the first time, this study demonstrates that a parenchymal factor, RAGE, mediates lung-specific accumulation of ILC2s.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据