Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Peter C. Cook, Sheila L. Brown, Emma L. Houlder, Julio Furlong-Silva, Daniel P. Conn, Stefano A. P. Colombo, Syed Baker, Freya R. Svedberg, Gareth Howell, Margherita Bertuzzi, Louis Boon, Joanne E. Konkel, Christopher R. Thornton, Judith E. Allen, Andrew S. MacDonald
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Abstract

Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c+ DCs and CD4+ T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+ cDC2s and CCR7+ DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2+ cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.

Abstract Image

Mgl2+ cDC2s在小鼠中协调真菌过敏性气道2型炎症,但不协调17型炎症
真菌孢子在环境中大量存在,是哮喘的主要原因。最初的特征是2型炎症性疾病,哮喘基础的过敏性气道炎症也可能涉及17型炎症,这可能加剧疾病,导致专门抑制2型因子的治疗失败。然而,决定宿主对真菌反应的机制尚不清楚,真菌可以引发过敏性气道疾病中的2型和17型炎症。在这里,我们发现CD11c+ dc和CD4+ T细胞对于反复暴露于吸入孢子的小鼠的2型和17型气道炎症的发展至关重要。单细胞rna测序和进一步的多参数细胞术显示,过敏性炎症显著改变了肺中众多DC簇的比例,但其中只有两个(Mgl2+ cDC2s和CCR7+ DC)迁移到dln。靶向去除几个DC亚群显示Mgl2+ cDC2缺失可减少2型真菌过敏性气道炎症,但不能减少17型真菌过敏性气道炎症。这些数据突出了不同的DC亚群作为治疗肺部真菌疾病的潜在治疗靶点。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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