Skin-associated B cells in allergy

过敏中的皮肤相关 B 细胞

• 批准号: 10088409
• 负责人: Loren D Erickson
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10088409
• 关键词: Acute; Affect; Allergens; Allergic; Allergic Disease; Allergic Reaction; Animals; Antibodies; Antibody Formation; Antigens; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Blood Group Antigens; Blood specimen; CCR6 gene; Cell Lineage; Cells; Characteristics; Chimera organism; Chronic; Chronic Disease; Consumption; Control Animal; Cutaneous; Data; Development; Disease; Eating; Exhibits; Exposure to; Food; Food Hypersensitivity; Functional disorder; Galactose; Gene Expression; Genes; Genetic; Genetic Transcription; Health; Heterogeneity; Human; Hypersensitivity; IgE; Immune; Immunoglobulin Class Switching; Immunoglobulin D; Immunoglobulin M; In Vitro; Individual; Infection; Inflammation; Kinetics; Lead; Life; Link; Maintenance; Meat; Mediating; Memory; Memory B-Lymphocyte; Mus; Oral Ingestion; Outcome Study; Pathogenesis; Pathology; Pathway interactions; Patients; Phenotype; Plasma; Plasma Cells; Play; Population; Prevalence; Production; Public Health; Reaction; Reporter; Resolution; Risk; Role; Site; Skin; Societies; Structure of germinal center of lymph node; System; Testing; Thinking; Ticks; Tissues; United States; alpha-gal syndrome; base; beef; chronic inflammatory disease; design; dietary; dimensional analysis; effective therapy; gastrointestinal; high dimensionality; high risk; insight; mouse model; novel; prevent; respiratory; skin barrier; targeted treatment; tick bite; tool; transcriptome; treatment strategy

Project Abstract A number of human chronic inflammatory diseases caused by infection, autoimmunity and allergy are strongly linked to B cells that infiltrate the skin, yet the precise role of skin-associated B cells in disease pathogenesis remains unclear. In particular, the underlying mechanisms by which skin exposure to allergens leads to the development and maintenance of IgE production has not been investigated, and a direct contribution by disease-specific B cells to inflammation and allergic reactions in tissue sites such as skin remains to be fully explored. In the studies proposed here we will characterize an expanded population of B cells found in skin of patients with food allergy to red meat and in a novel mouse model of meat allergy our lab recently developed. We will explore the kinetics and phenotype of CCR6hi B cells that accumulate in inflamed skin, evaluate the specific contribution of CCR6hi B cells to disease as well as their function as allergen-specific IgE-producing cells. These efforts will provide a broad assessment of the features and potential functions of this highly expanded B cell population in human allergy.

项目摘要 许多由感染、自身免疫和变态反应引起的人类慢性炎症性疾病， 与浸润皮肤的B细胞有关，但皮肤相关B细胞在疾病发病机制中的确切作用 仍不清楚特别是，皮肤暴露于过敏原导致过敏的潜在机制， 还没有研究IgE产生的发展和维持， 疾病特异性B细胞对组织部位如皮肤中的炎症和过敏反应的作用仍有待充分研究。 探讨了在这里提出的研究中，我们将描述在皮肤中发现的B细胞的扩增群体， 对红肉食物过敏的患者和我们实验室最近开发的肉类过敏的新小鼠模型。 我们将探索CCR6 hi B细胞在发炎皮肤中的聚集动力学和表型，评估CCR6 hi B细胞在炎症皮肤中的表达。 CCR6 hi B细胞对疾病的特异性贡献以及它们作为变应原特异性IgE产生细胞的功能 细胞这些努力将提供一个广泛的评估的特点和潜在的功能，这一高度 扩增的B细胞群在人类变态反应中的作用。