Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines
Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines
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DOI：
10.1073/pnas.1112268109
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发表时间：
2012-04-24
影响因子：
11.1
通讯作者：
Hartmann, Susanne
中科院分区：
文献类型：
--
作者：
Hepworth, Matthew R.;Danilowicz-Luebert, Emilia;Hartmann, Susanne
肥大细胞（MC）是分布于整个粘膜屏障组织中的强效炎性细胞，对病原刺激反应迅速。在蠕虫感染过程中，MC作为晚期效应物发挥重要作用。然而，目前尚不清楚MC是否有助于决定适应性免疫启动的早期先天事件。MC-缺陷小鼠品系和MC稳定剂克罗维甲酸钠处理的小鼠显著降低了Th 2启动和2型细胞因子的产生，并在感染胃肠道蠕虫（Heligmosomoides polygyrus bakeri和Trichuris muris）后增加了寄生虫负担。此外，在MC缺陷小鼠中，组织来源的细胞因子IL-25、IL-33和胸腺基质淋巴细胞生成素（TSLP）的早期产生显著减少，并导致感染诱导的IL-25依赖性（Lin（-）CD 45（-））CD 34（+）Sca-1（+）祖细胞数量减少，这些祖细胞产生2型细胞因子，并可在体外分化为肥大细胞。最后，MC缺陷的修复增加了IL-25、IL-33和TSLP的产生，恢复了祖细胞数量和Th 2启动，并减少了寄生虫负担。我们的数据揭示了MCs在通过调节IL-25、IL-33和TSLP协调2型免疫应答中的先天IgE非依赖性作用。
Mast cells (MCs) are potent inflammatory cells that are distributed throughout mucosal barrier tissues and respond rapidly to pathogenic stimuli. During helminth infections, MCs play an important role as late-stage effectors. However, it is currently unknown whether MCs contribute to the early innate events that determine the priming of adaptive immunity. MC-deficient mouse strains and mice treated with the MC stabilizing agent cromolyn sodium had dramatically reduced Th2 priming and type 2 cytokine production and harbored increased parasite burdens following infection with gastrointestinal helminths (Heligmosomoides polygyrus bakeri and Trichuris muris). In addition, early production of the tissue-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) was significantly diminished in MC-deficient mice and resulted in decreased numbers of infection-elicited IL-25-dependent (Lin(-)CD45(-))CD34(+)Sca-1(+) progenitors, which produced type 2 cytokines and could be differentiated into mast cells ex vivo. Finally, repair of MC deficiency increased production of IL-25, IL-33, and TSLP, restored progenitor cell numbers and Th2 priming, and reduced parasite burden. Our data reveal an innate IgE-independent role for MCs in orchestrating type 2 immune responses via the regulation of IL-25, IL-33, and TSLP.