ILC3s control airway inflammation by limiting T cell responses to allergens and microbes.

ILC3s control airway inflammation by limiting T cell responses to allergens and microbes.
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ILC3通过限制T细胞对过敏原和微生物的反应来控制气道炎症。

DOI:
10.1016/j.celrep.2021.110051
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发表时间:
2021-11-23
期刊:
影响因子:
8.8
通讯作者:
Sonnenberg GF
Sonnenberg GF
中科院分区:
生物学1区
文献类型:
--
作者:
Teng F;Tachó-Piñot R;Sung B;Farber DL;Worgall S;Hammad H;Lambrecht BN;Hepworth MR;Sonnenberg GF

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第3组先天淋巴样细胞(ILC3s)在胃肠道中对宿主-微生物的相互作用起着关键的调节作用,但它们在气道中的作用仍然知之甚少。在这里,我们证明了淋巴组织诱导剂(LTi)样ILC3s在健康小鼠和人类的肺引流淋巴结中富集。这些ILC3s大量表达主要组织相容性复合体II类(MHC II类),并在实验性气道攻击时功能上限制过敏原特异性CD4+ T细胞的扩增。在屋尘螨诱导的过敏性气道炎症小鼠模型中,MHC II类+ ILC3s限制T辅助型2 (Th2)细胞反应、嗜酸性粒细胞增多和气道高反应性。此外,MHC II类+ ILC3s限制了伴随的Th17细胞反应和气道嗜中性粒细胞。这种加剧的Th17细胞反应需要将肺部暴露于微生物刺激下,这与室内尘螨有关。这些发现表明抗原呈递ILC3s通过限制促炎T细胞对过敏原和微生物的反应,在协调气道免疫耐受中起关键作用。在这项研究中,Teng等人证明了一种先天免疫细胞类型ILC3在健康人和小鼠的肺引流淋巴结中富集,并通过抗原呈递和控制针对过敏原或微生物的T细胞反应来限制气道炎症。
Group 3 innate lymphoid cells (ILC3s) critically regulate host-microbe interactions in the gastrointestinal tract, but their role in the airway remains poorly understood. Here, we demonstrate that lymphoid-tissue-inducer (LTi)-like ILC3s are enriched in the lung-draining lymph nodes of healthy mice and humans. These ILC3s abundantly express major histocompatibility complex class II (MHC class II) and functionally restrict the expansion of allergen-specific CD4+ T cells upon experimental airway challenge. In a mouse model of house-dust-mite-induced allergic airway inflammation, MHC class II+ ILC3s limit T helper type 2 (Th2) cell responses, eosinophilia, and airway hyperresponsiveness. Furthermore, MHC class II+ ILC3s limit a concomitant Th17 cell response and airway neutrophilia. This exacerbated Th17 cell response requires exposure of the lung to microbial stimuli, which can be found associated with house dust mites. These findings demonstrate a critical role for antigen-presenting ILC3s in orchestrating immune tolerance in the airway by restricting pro-inflammatory T cell responses to both allergens and microbes. In this study, Teng et al. demonstrate that an innate immune cell type, ILC3, is enriched in the lung draining lymph node of healthy humans and mice and functions to limit airway inflammation through antigen presentation and control of T cell responses directed against allergens or microbes.
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