Tissue Regulation of T Cell Function

T 细胞功能的组织调节

• 批准号: 10689168
• 负责人: Deborah J Fowell
• 金额: $ 241.62万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689168
• 关键词: Address; Adhesions; Antigen-Presenting Cells; Apoptosis; Architecture; Autoimmune; B-Lymphocytes; Behavior; Blood Vessels; CD8-Positive T-Lymphocytes; Cardiovascular Diseases; Cell physiology; Cells; Cessation of life; Complex; Cues; Custom; Cutaneous; EGF gene; Educational workshop; Effector Cell; Environment; Event; Funding; Generations; Genetic Transcription; Goals; Homing; Image; Image Analysis; Immune; Immune response; Immunity; In Situ; Infection; Inflammation; Inflammatory Response; Influenza; Knowledge; Leukocytes; Lung; Lymphoid Tissue; Macrophage; Measures; Mechanics; Mediator; Memory; Molecular; Mus; Pathology; Peripheral; Positioning Attribute; Process; Reagent; Resolution; Shapes; Signal Transduction; Site; Skin; Skin Tissue; Structure of parenchyma of lung; System; T cell differentiation; T cell regulation; T-Cell Activation; T-Lymphocyte; Time; Tissues; Visualization; cell motility; cell type; chemokine; cytokine; differential expression; effector T cell; first responder; imaging platform; immune function; inflammatory milieu; influenza infection; innovation; insight; interstitial; intravital imaging; lymph nodes; meetings; migration; neutrophil; novel; pathogen; programs; quantitative imaging; recruit; release factor; response; symposium; therapeutic target; tissue repair; tool

PROJECT SUMMARY/ABSTRACT – OVERALL Pathogen infection initiates local inflammation that leads to the influx of innate effector cells and elaboration of chemokines, cytokines and other soluble mediators. T effector cells entering the infected tissue encounter a tissue environment that has been differentially altered from the basal state depending on the type of pathogen and corresponding innate inflammatory response. Effector T cells must migrate through this interstitial space to locate antigen-presenting cells and infected target cells and receive activation signals for effector function, pathogen clearance and establishment of tissue memory. Although the framework of these complex interactions between innate cells, soluble mediators and tissue architecture is established, the ability of effector T cells to sense and interpret different inflammatory environments and the impact on immune function are poorly understood. Yet, it is within the infected peripheral tissues that they must execute their effector function for pathogen clearance. It is also within peripheral tissues where dysregulated inflammation leads to immune pathology; from autoimmune to cardio-vascular disease. Using innovative tools for in situ modulation and visualization of immune responses in the skin and lung of the mouse the goal of this Program Project is to gain insight into the signals that control T cell recruitment, migration and activation in infected or inflamed tissues of the skin and lung. The previous funding cycle has identified new mechanisms of T cell recruitment, interstitial migration, and positioning of effector and tissue memory subsets. This proposal builds on these molecular checkpoints at sites of inflammation to determine how external signals from innate cells and the tissue microenvironment shape the position and function of effector T cells for protective immunity. Project 1. Resolution of neutrophil response for effective T cell functions and tissue repair. Dr Minsoo Kim. Hypothesis: that neutrophil death is not passive, but rather, that the release of specific factors from dying neutrophils promotes effective T cell activation and tissue repair. Project 2. Spatial optimization of T cell activation at inflamed sites via cytokine/chemokine-dependent cellular clustering. Dr Deborah Fowell. Hypothesis: that peripheral T cell activation occurs in chemokine-rich peri-vascular clusters that nucleate and amplify T cell recruitment/activation for efficient pathogen clearance. Project 3. Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection. Dr David Topham. Hypothesis: specific TRM subsets occupy distinct spatial microenvironments in the airway that confer functional differences in protection against influenza infection. Project 4. Mechanics of T cell migration. Dr Patrick Oakes. Hypothesis: that migration of different immune cells lies along a single continuum, differing only in relative contributions of adhesion and force generation. Core A. Administrative, Fowell D.J.; Core B. Imaging, Kim M.; Core C. Reagents, Miller J.

项目摘要/摘要-总体

项目成果

Nonmuscle myosin 2 filaments are processive in cells

非肌肉肌球蛋白 2 丝在细胞中持续进行

• DOI: 10.1016/j.bpj.2023.05.014
• 发表时间: 2023
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Vitriol, Eric A.;Quintanilla, Melissa A.;Tidei, Joseph J.;Troughton, Lee D.;Cody, Abigail;Cisterna, Bruno A.;Jane, Makenzie L.;Oakes, Patrick W.;Beach, Jordan R.
• 通讯作者: Beach, Jordan R.

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19.

• DOI: 10.1038/s41577-020-00470-2
• 发表时间: 2021-01
• 期刊: Nature reviews. Immunology
• 作者: Alon R;Sportiello M;Kozlovski S;Kumar A;Reilly EC;Zarbock A;Garbi N;Topham DJ
• 通讯作者: Topham DJ

Formation and Maintenance of Tissue Resident Memory CD8+ T Cells after Viral Infection.

病毒感染后组织驻留记忆 CD8 T 细胞的形成和维持。

• DOI: 10.3390/pathogens8040196
• 发表时间: 2019
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Topham,DavidJ;Reilly,EmmaC;Emo,KrisLambert;Sportiello,Mike
• 通讯作者: Sportiello,Mike

Metabolic Challenges in Anticancer CD8 T Cell Functions.

• DOI: 10.4110/in.2023.23.e9
• 发表时间: 2023-03
• 期刊: IMMUNE NETWORK
• 影响因子: 6
• 作者: Amitrano, Andrea M.;Kim, Minsoo
• 通讯作者: Kim, Minsoo

Intravital three-photon microscopy allows visualization over the entire depth of mouse lymph nodes.

• DOI: 10.1038/s41590-021-01101-1
• 发表时间: 2022-03
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Choe, Kibaek;Hontani, Yusaku;Wang, Tianyu;Hebert, Eric;Ouzounov, Dimitre G.;Lai, Kristine;Singh, Ankur;Beguelin, Wendy;Melnick, Ari M.;Xu, Chris
• 通讯作者: Xu, Chris