Development and function of inflammatory innate lymphoid cells

炎症先天淋巴细胞的发育和功能

• 批准号: 10533596
• 负责人: Qi yang
• 金额: $ 23.63万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10533596
• 关键词: Development; function; inflammatory; innate; lymphoid

Project Summary/Abstract The goal of this project is to understand the mechanisms that control effector lymphocyte stability and plasticity, and how this regulation influences human health and disease. Recent studies indicate that innate lymphocytes possess substantial plasticity. The underlying mechanisms, and the implications for health and disease, remain unknown. Our preliminary data indicate that exposure to Notch signaling can elicit innate lymphocyte plasticity and train mature group-2 innate lymphoid cells (ILC2) to acquire the ability to co-produce large amounts of both ILC2- and ILC3- characteristic cytokines, thus converting natural ILC2 (nILC2) into plastic inflammatory ILC2 (iILC2). Our new data suggest that such plastic iILC2 are relatively enriched in the airway of patients with severe refractory asthma. In this project, we will use adoptive transfer, chromatin immunoprecipitation, and RNA sequencing experiments to explore the cellular and molecular mechanisms by which Notch signaling elicits ILC2 plasticity. We will also examine the capability of human and mouse iILC2 to mediate airway inflammation and hyperresponsiveness. Finally, we will investigate the association between the development of plastic iILC2 and the susceptibility to severe refractory asthma in human adult patients. Together, these experiments will shed light on the mechanisms that govern lymphocyte lineage stability and plasticity, and will inform strategies of targeted therapy to treat patients with asthma and other auto-immune and inflammatory disorders.

项目概要/摘要 该项目的目标是了解控制效应淋巴细胞稳定性和 可塑性，以及这种调节如何影响人类健康和疾病。最近的研究表明，先天 淋巴细胞具有很强的可塑性。基本机制以及对健康和健康的影响 疾病，仍不明。我们的初步数据表明，暴露于 Notch 信号传导可以引发先天性的 淋巴细胞可塑性并训练成熟的第 2 组先天淋巴细胞 (ILC2) 以获得共同产生的能力 大量 ILC2 和 ILC3 特征细胞因子，从而将天然 ILC2 (nILC2) 转化为 塑料炎症 ILC2 (iILC2)。我们的新数据表明，此类塑料 iILC2 在以下方面相对丰富： 严重难治性哮喘患者的气道。在这个项目中，我们将使用过继转移、染色质 免疫沉淀和RNA测序实验探索细胞和分子机制 Notch 信号传导引发 ILC2 可塑性。我们还将检查人类和小鼠 iILC2 的能力 介导气道炎症和高反应性。最后，我们将研究两者之间的关联 可塑性 iILC2 的发育和成人患者对严重难治性哮喘的易感性。 总之，这些实验将揭示控制淋巴细胞谱系稳定性和 可塑性，并将为治疗哮喘和其他自身免疫性疾病患者的靶向治疗策略提供信息 和炎症性疾病。

项目成果

Adventitial stromal cells and myofibroblasts recruit pro- and anti-inflammatory immune cells in allergic airway inflammation.

外膜基质细胞和肌成纤维细胞在过敏性气道炎症中招募促炎和抗炎免疫细胞。

• DOI: 10.1111/all.15766
• 发表时间: 2023
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Xu,En;Cao,Gaoyuan;Yang,Zhi;Zhang,Yuanyue;Si,Youwen;Singh,Kunal;Jude,Joseph;An,StevenS;Koziol-White,CynthiaJ;PanettieriJr,ReynoldA;Yang,Qi
• 通讯作者: Yang,Qi

Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function.

• DOI: 10.1038/s41590-022-01349-1
• 发表时间: 2022-12
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Zhang, Yuanyue;Bailey, Jacob T.;Xu, En;Singh, Kunal;Lavaert, Marieke;Link, Verena M.;D'Souza, Shanti;Hafiz, Alex;Cao, Jian;Cao, Gaoyuan;Sant'Angelo, Derek B.;Sun, Wei;Belkaid, Yasmine;Bhandoola, Avinash;McGavern, Dorian B.;Yang, Qi
• 通讯作者: Yang, Qi

Type I Interferon signaling controls the accumulation and transcriptomes of monocytes in the aged lung.

• DOI: 10.1111/acel.13470
• 发表时间: 2021-10
• 期刊: Aging cell
• 影响因子: 7.8
• 作者: D'Souza SS;Zhang Y;Bailey JT;Fung ITH;Kuentzel ML;Chittur SV;Yang Q
• 通讯作者: Yang Q

Group 2 innate lymphoid cells are numerically and functionally deficient in the triple transgenic mouse model of Alzheimer's disease.

• DOI: 10.1186/s12974-021-02202-2
• 发表时间: 2021-07-06
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Fung ITH;Zhang Y;Shin DS;Sankar P;Sun X;D'Souza SS;Song R;Kuentzel ML;Chittur SV;Zuloaga KL;Yang Q
• 通讯作者: Yang Q