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.

项目总结/文摘

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

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

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

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