The role of tissue-resident T cells in resolving inflammation of the human oral mucosa

组织驻留 T 细胞在解决人类口腔粘膜炎症中的作用

• 批准号: 10625076
• 负责人: Douglas Dixon
• 金额: $ 61.53万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2024-08-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10625076
• 关键词: Address; Affect; Anti-Inflammatory Agents; Antigen-Presenting Cells; Biological Assay; Biological Markers; Blood; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell Compartmentation; Cell physiology; Cells; Characteristics; Chronic; Clinical Trials; Coculture Techniques; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; Dentition; Disease; Ensure; Etiology; Failure; Flow Cytometry; Gingiva; Goals; Health; Homeostasis; Hour; Human; Immune; Immune Targeting; Immune system; Immunity; Immunologics; In Situ; In Vitro; Inflammation; Inflammatory; Interleukin-17; Longevity; Lymph; Mucous Membrane; Myeloid-derived suppressor cells; Operative Surgical Procedures; Oral; Oral Surgical Procedures; Oral health; Oral mucous membrane structure; Pathology; Periodontium; Phenotype; Population; Process; Property; Regulatory T-Lymphocyte; Reporting; Resolution; Role; Science; Signal Transduction; Site; Stimulus; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Textbooks; Time; Tissues; antagonist; bone loss; chemokine receptor; effector T cell; exhaust; experimental study; human tissue; immune function; insight; interleukin-22; loss of function; macrophage; monocyte; novel therapeutic intervention; oral tissue; preservation; prevent; programmed cell death protein 1; receptor; recruit; regeneration function; repair function; repaired; therapeutic target; tissue repair

Project Summary Tissue destruction and bone loss occur due to uncontrolled and progressing inflammation within gingival tissue. Resolution of inflammation is necessary to return to a homeostatic state and to initiate reparative/regenerative functions within mucosal tissues. We examined chronically inflamed gingival tissues to determine if T cells with anti-inflammatory function (regulatory T cells; Treg) and tissue-repair function (IL-17 and IL-22 secreting T cells; Th17/22) are lost or preserved during inflammation. We found that Treg and Th17/22 CD4 T cell populations were still intact in the inflamed gingiva suggesting that there is a retained intrinsic ability to resolve inflammation. We now propose to interrogate different mechanisms that could interfere with Th17/22 and Treg promoted resolution of inflammation. Of note, some IL-17 is critical to maintain barrier immunity, while excess IL-17 drives tissue pathology, thus the presence Th17 cells must be interpreted carefully and in context of the T cell population. We consider and propose to test several different possibilities: tissue damaging effector T cells may counteract ongoing repair efforts, Treg and Th17/22 functions may not be properly elicited in the inflamed gingiva and repair efforts may be actively suppressed by APCs. The goal of our proposed experiments is to gain a better understanding of the immunological mechanisms that perpetuate a state of inflammation and prevent resolution of inflammation in chronically inflamed gingiva. Identifying these immunological mechanisms is relevant as it will help provide insight to ultimately allow for selective therapeutic targeting of immune cell subsets to treat chronically inflamed oral tissues.

项目摘要 组织破坏和骨丢失发生由于不受控制和进展性炎症内牙龈 组织.炎症的消退对于恢复稳态和启动 粘膜组织内的修复/再生功能。我们检查了慢性发炎的牙龈组织， 确定具有抗炎功能的T细胞（调节性T细胞; Treg）和组织修复功能（IL-17）是否 和分泌IL-22的T细胞; Th 17/22）在炎症期间丢失或保留。我们发现Treg和 Th 17/22 CD 4 T细胞群在发炎的牙龈中仍然完整，这表明存在保留的 解决炎症的内在能力。我们现在建议询问不同的机制， 干扰Th 17/22和Treg促进炎症消退。值得注意的是，一些IL-17对于维持 屏障免疫，而过量的IL-17驱动组织病理，因此必须解释Th 17细胞的存在 仔细地并且在T细胞群体的背景下。我们考虑并建议测试几种不同的可能性： 组织损伤效应T细胞可能会抵消正在进行的修复努力，Treg和Th 17/22功能可能不会 在发炎的牙龈中适当地引发，并且修复努力可以被APC积极地抑制。的目标 我们提出的实验是为了更好地了解使免疫系统永久化的免疫机制， 一种炎症状态，并阻止慢性炎症牙龈的炎症消退。识别这些 免疫机制是相关的，因为它将有助于提供见解，以最终允许选择性治疗 靶向免疫细胞亚群以治疗慢性发炎的口腔组织。