Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity.
Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity.
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肥胖与哮喘的发展和相当多的哮喘相关医疗保健利用有关。为了了解导致肥胖相关哮喘的免疫途径，我们给小鼠喂食了12周的高脂肪饮食，这导致了肥胖和气道高反应性（AHR）的发展，这是哮喘的一个主要特征。这种AHR依赖于先天免疫，因为它发生在肥胖的Rag - / -小鼠中，而依赖于IL-17A和NLRP3炎性体，因为它不发生在肥胖的Il17 - / -或NLRP3 - / -小鼠中。AHR还与CCR6+先天淋巴样细胞肺中产生IL-17A （ILC3细胞）的存在有关，IL-17A在过继转移到Rag2−/−Il2rγ−/−小鼠时可以通过自身介导AHR。IL-1β通过扩大ILC3细胞发挥重要作用，阻断IL-1β功能的治疗可消除肥胖诱导的AHR。由于我们在哮喘患者的支气管肺泡灌洗液中发现了ILC3样细胞，我们认为NLRP3、IL-1β和ILC3细胞介导的炎症促进了肥胖相关哮喘的发生。
Obesity is associated with the development of asthma and considerable asthma-related healthcare utilization. To understand the immunological pathways that lead to obesity-associated asthma, we fed mice a high fat diet for 12 weeks, which resulted in obesity and the development of airway hyperreactivity (AHR), a cardinal feature of asthma. This AHR depended on innate immunity, since it occurred in obese Rag−/− mice, and on IL-17A and the NLRP3 inflammasome, since it did not develop in obese Il17−/− or Nlrp3−/− mice. The AHR was also associated with the presence in the lungs of CCR6+ innate lymphoid cells producing IL-17A (ILC3 cells), which could by themselves mediate AHR when adoptively transferred into Rag2−/− Il2rγ−/− mice. IL-1β played an important role by expanding the ILC3 cells, and treatment to block the function of IL-1β abolished obesity-induced AHR. Since we found ILC3-like cells in the bronchoalveolar lavage fluid of human patients with asthma, we suggest that obesity-associated asthma is facilitated by inflammation mediated by NLRP3, IL-1β and ILC3 cells.
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DOI：
10.4049/jimmunol.1102488
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Allen IC;Jania CM;Wilson JE;Tekeppe EM;Hua X;Brickey WJ;Kwan M;Koller BH;Tilley SL;Ting JP
通讯作者：
Ting JP
影响因子：
29
作者：
Arteaga-Solis E;Zee T;Emala CW;Vinson C;Wess J;Karsenty G
通讯作者：
Karsenty G
DOI：
10.1016/j.jaci.2011.03.036
发表时间：
2011-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Holguin F;Bleecker ER;Busse WW;Calhoun WJ;Castro M;Erzurum SC;Fitzpatrick AM;Gaston B;Israel E;Jarjour NN;Moore WC;Peters SP;Yonas M;Teague WG;Wenzel SE
通讯作者：
Wenzel SE
DOI：
10.1164/rccm.200702-323oc
发表时间：
2007-10-01
影响因子：
24.7
作者：
Johnston, Richard A.;Zhu, Ming;Shore, Stephanie A.
通讯作者：
Shore, Stephanie A.
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio