Functional mechanisms of CCR10 in maintenance of the skin immune homeostasis

CCR10维持皮肤免疫稳态的功能机制

• 批准号: 9127792
• 负责人: NA XIONG
• 金额: $ 38.87万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127792
• 关键词: Animal Model; Antigens; Atopic Dermatitis; Biological; CCL27 gene; CD8B1 gene; Cell Maintenance; Cell physiology; Cells; Chemicals; Chronic; Cutaneous; Defect; Development; Disease; Ensure; Epithelial; Equilibrium; Eragrostis; Functional disorder; GPR2 gene; Health; Homeostasis; Homing; Immune; Immune response; Immune system; Individual; Inflammation; Inflammatory; Knock-in; Knock-in Mouse; Knock-out; Knockout Mice; Ligands; Maintenance; Malignant Neoplasms; Mediating; Memory; Modeling; Molecular; Mus; Pathology; Phase; Play; Process; Psoriasis; Public Health; Regulation; Regulatory T-Lymphocyte; Reporter; Resolution; Role; Skin; Syndrome; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Tissues; antigen challenge; assault; base; chemokine receptor; design; in vivo; keratinocyte; migration; mouse model; novel; prevent; receptor; response; skin disorder; therapeutic target

DESCRIPTION (provided by applicant): Summary CCR10 is a chemokine receptor. One of its ligand, CCL27, is predominantly expressed in the skin. The CCR10/ligand axis was suggested to play a role in directing migration and maintenance of CCR10-expressing T cells into the skin and has been implicated in many skin inflammatory diseases such as psoriasis and atopic dermatitis. However, the in vivo functional importance and mechanisms of CCR10 in regulating the cutaneous immune responses are still not clear. We have generated CCR10-knockout/EGFP-knockin mice and found that the CCR10-knockout mice have altered maintenance of skin-resident T cells and response to various skin antigen challenges. We propose to use these mouse models to study the functional mechanisms of CCR10 in regulating the skin T response and immune homeostasis.

CCR10是一种趋化因子受体。其中一种配体CCL27主要在皮肤中表达。CCR10/配体轴被认为在指导表达CCR10的T细胞向皮肤的迁移和维持中发挥作用，并与许多皮肤炎症性疾病（如牛皮癣和特应性皮炎）有关。然而，CCR10在调节皮肤免疫应答中的体内功能重要性和机制尚不清楚。我们培育了ccr10敲除/ egfp敲除小鼠，发现ccr10敲除小鼠改变了皮肤常驻T细胞的维持和对各种皮肤抗原挑战的反应。我们建议利用这些小鼠模型来研究CCR10在调节皮肤T反应和免疫稳态中的功能机制。