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- Title
IL-10-producing lung interstitial macrophages prevent neutrophilic asthma.
- Authors
Hideo Kawano; Hisako Kayama; Takekuni Nakama; Takashi Hashimoto; Eiji Umemoto; Kiyoshi Takeda
- Abstract
Inflammatory responses contribute to host defense against harmful organisms and allergens, whereas a failure of immune tolerance can cause chronic inflammation including asthma. The lung has several innate myeloid cell subsets. Among these subsets, there are two types of macrophages: alveolar macrophages (AMs) and interstitial macrophages (IMs). However, compared with AMs, the role of IMs in lung homeostasis remains poorly understood. In this study, we characterized AMs and IMs in healthy and inflammatory conditions. Pulmonary IMs constitutively produce the anti-inflammatory cytokine IL-10 through activation of the TLR4/MyD88 pathway in a microbiotaindependent manner. In addition to IMs, Foxp3+ Treg cells show persistent IL-10 expression in the lung, with IL-10-producing IMs more prevalent than Foxp3+ Treg cells. IMs, but not Foxp3+ Treg cells, increased IL-10 production in house dust mite (HDM)-challenged mice, a model of human asthma. HDM-challenged Il10-/- mice exhibited severe lung pathology characterized by neutrophilia compared with that of wild-type mice. In addition, transplantation of wild-type IMs reduced neutrophilic inflammation, goblet cell mucus production and decreased expression of lung IL-13 and Th17- related neutrophil-activating cytokines such as IL-17, GM-CSF, and TNF-α. Together these results demonstrate that IL-10-producing IMs negatively regulate Th2- and Th17-mediated inflammatory responses, helping prevent neutrophilic asthma.
- Subjects
MACROPHAGES; NEUTROPHILS; ASTHMA prevention; INFLAMMATION; CYTOKINE industry; HOUSE dust mites
- Publication
International Immunology, 2016, Vol 28, Issue 10, p489
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxw012