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UNIQUE ROLES OF ANTIGEN PRESENTING CELLS ON T CELL TOLERANCE AND AUTOIMMUNITY

抗原呈递细胞对 T 细胞耐受和自身免疫的独特作用

基本信息

批准号：
10238938
负责人：
CHYI S HSIEH
金额：
$ 42.54万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-25 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238938
关键词：
Affect American Antigen Presentation Antigen Targeting Antigen-Presenting Cells Antigens Autoantigens Autoimmune Autoimmune Diseases Autoimmunity B-Lymphocytes Bone Marrow Bone Marrow Transplantation CD36 gene CD8-Positive T-Lymphocytes Cell Differentiation process Cell surface Cells Clinical Clone Cells Data Dendritic Cells Development Diagnostic tests Disease Education Effector Cell Environment Equilibrium FOXP3 gene Generations Goals Grant Homeostasis Immune Immunity Immunology Knowledge Lead Learning Left Maintenance Malignant Neoplasms Manuscripts Mediating Mus Pathway interactions Peripheral Play Prevention Process Publishing Regulatory T-Lymphocyte Rest Role Science Self Tolerance Specificity Surface Antigens T cell differentiation T-Lymphocyte T-cell receptor repertoire Testing Th1 Cells Thymic epithelial cell Thymus Gland Tissues antigen-specific T cells autoreactive T cell human disease insight novel novel therapeutics response transcription factor

项目摘要

7. Project Summary/Abstract The development of both tolerance and autoimmunity is dependent on the presentation of self-antigens in the thymus and periphery. Thymic tolerance requires recognition of self-antigens leading to negative selection, i.e. deletion of self-reactive T cell clones; or selection into Foxp3+ regulatory T (Treg) cells, important for maintaining immune homeostasis in the periphery. In the periphery, presentation of self-antigens results in maintenance and induction of regulatory T cells to promote tolerance, but can also facilitate autoimmunity via induction of self-reactive effector cells. These processes are driven by antigen presenting cells (APCs), of which there are several subsets. Previously, we showed that Batf3-dependent CD8α+ DCs play an important role in thymic tolerance as the major recipient of antigen transfer from medullary thymic epithelial cells (mTECs), which produce a variety of self-antigens via the effect of the transcription factor Aire. Here, we propose to continue our studies on the role of CD8α+ DCs in tolerance and autoimmunity. We will continue our ongoing studies of thymic CD8α+ DCs with the goal of understanding the mechanisms of antigen transfer (Aim 1). We will also ask whether CD8α+ DCs present a unique array of self-antigens in the periphery with the goal of identifying the origin of some of these antigens (Aim 2). Finally, we will determine whether peripheral CD8α+ DCs are involved in effector vs regulatory T cell differentiation in response to self-antigens (Aim 3). If successful, this grant will offer new insights regarding the role of CD8α+ DCs in providing antigen-specific and T cell developmental niches in the thymus and periphery that may control the balance between tolerance and autoimmunity.

7. 项目总结/文摘

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intraclonal competition limits the fate determination of regulatory T cells in the thymus.

DOI：
10.1038/ni.1739
发表时间：
2009-06
期刊：
Nature immunology
影响因子：
30.5
作者：
通讯作者：

CD28 facilitates the generation of Foxp3(-) cytokine responsive regulatory T cell precursors.

DOI：
10.4049/jimmunol.1000019
发表时间：
2010-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Lio CW;Dodson LF;Deppong CM;Hsieh CS;Green JM
通讯作者：
Green JM

T cell tolerance and immunity to commensal bacteria.

DOI：
10.1016/j.coi.2012.04.009
发表时间：
2012-08
期刊：
Current opinion in immunology
影响因子：
7
作者：
Nutsch KM;Hsieh CS
通讯作者：
Hsieh CS

Peripheral education of the immune system by colonic commensal microbiota.

DOI：
10.1038/nature10434
发表时间：
2011-09-21
期刊：
NATURE
影响因子：
64.8
作者：
Lathrop, Stephanie K.;Bloom, Seth M.;Rao, Sindhuja M.;Nutsch, Katherine;Lio, Chan-Wang;Santacruz, Nicole;Peterson, Daniel A.;Stappenbeck, Thaddeus S.;Hsieh, Chyi-Song
通讯作者：
Hsieh, Chyi-Song

MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells.