Roles and therapeutic potential of CD150high niche-associated regulatory T cells in bone marrow injury and engraftment
Roles and therapeutic potential of CD150high niche-associated regulatory T cells in bone marrow injury and engraftment
批准号:
10322010
负责人:
Joji Fujisaki
金额:
$28.51万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-08-15 至 2023-05-31
中文摘要
项目摘要
英文摘要
Project Abstract
Although the stem cell microenvironment, or the niche, has been extensively studied as a site which regulates
stem cell functions, immunological attributes of the niche have been largely unexplored. Interestingly, studies
conducted over six decades ago revealed that the locations of germline and embryonic stem cells, the testis
and placenta, immunological sanctuaries for stem cells, termed immune privileged (IP) sites. In these tissues,
transplanted allogeneic or xenogeneic grafts can persist without immune suppressive therapy, distinguishing IP
sites from other sites. Little is known about whether tissue-committed stem cell niches serve as IP sites. Our
recent studies demonstrated evidence suggesting that the HSC niche within the bone marrow (BM) is an IP
site. We showed that unique FoxP3+ regulatory T cells (Tregs) with high expression of an HSC marker,
CD150, frequently localized adjacent to HSCs. These Tregs enabled persistence of allo-HSCs in non-
conditioned immune competent mice without immune suppression. In non-transplantation settings, niche Tregs
protected endogenous HSCs from oxidative stress, maintaining HSC quiescence. These observations suggest
that niche Tregs endow HSCs with immune privilege. To promote translation of our findings into clinical
settings, we will propose to study roles and therapeutic potential of niche Tregs in hematopoiesis failure
following irradiation and in allo-HSC engraftment following non-myeloablative conditioning. We will characterize
niche Tregs' stress-resistance, repopulating potential, molecular signatures, and T cell receptor (TCR)
repertoire, assessing how these features of niche Tregs contribute to HSC protection or engraftment.
Successful studies will identify unprecedented Treg subsets which act as stem cell protectants from immune
attack and stress within the niche, decipher mechanisms of this niche Treg-mediated stem cell protection or
engraftment, and lead to development of promising therapeutic strategies for post-irradiation BM injury or
engraftment by transferring or manipulating niche Tregs. Therefore, the results of our proposed studies will
eventually improve outcomes of allo-BM transplantation or radiation therapy for patients with blood disorders,
immune deficiency, metabolic diseases, blood malignancies, and solid cancers.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Identification of unique nitric oxide-expressing hematopoietic stem cells and their special vascular niche
-
批准号:10561727
-
项目类别:
-
资助金额:$45.97万
-
财政年份:2021
-
负责人:Joji Fujisaki
-
依托单位:
Identification of unique nitric oxide-expressing hematopoietic stem cells and their special vascular niche
-
批准号:10331423
-
项目类别:
-
资助金额:$34.48万
-
财政年份:2021
-
负责人:Joji Fujisaki
-
依托单位:
Privileged and primitive hematopoietic stem cells, niches, and regulatory T cells
-
批准号:10531890
-
项目类别:
-
资助金额:$77.41万
-
财政年份:2021
-
负责人:Joji Fujisaki
-
依托单位:
Privileged and primitive hematopoietic stem cells, niches, and regulatory T cells
-
批准号:10364110
-
项目类别:
-
资助金额:$77.41万
-
财政年份:2021
-
负责人:Joji Fujisaki
-
依托单位:
Identification of unique nitric oxide-expressing hematopoietic stem cells and their special vascular niche
-
批准号:10398258
-
项目类别:
-
资助金额:$43.3万
-
财政年份:2021
-
负责人:Joji Fujisaki
-
依托单位:
Identification of unique nitric oxide-expressing hematopoietic stem cells and their special vascular niche
-
批准号:9973669
-
项目类别:
-
资助金额:$42.55万
-
财政年份:2020
-
负责人:Joji Fujisaki
-
依托单位:
Roles and therapeutic potential of CD150high niche-associated regulatory T cells in bone marrow injury and engraftment
-
批准号:10163898
-
项目类别:
-
资助金额:$49.33万
-
财政年份:2019
-
负责人:Joji Fujisaki
-
依托单位:
Roles and therapeutic potential of CD150high niche-associated regulatory T cells in bone marrow injury and engraftment
-
批准号:10456272
-
项目类别:
-
资助金额:$49.33万
-
财政年份:2019
-
负责人:Joji Fujisaki
-
依托单位:
Immune privilege of the hematopoieitic stem cell niche
-
批准号:10322011
-
项目类别:
-
资助金额:$28.92万
-
财政年份:2016
-
负责人:Joji Fujisaki
-
依托单位:
Immune privilege of the hematopoieitic stem cell niche
-
批准号:9895853
-
项目类别:
-
资助金额:$11.08万
-
财政年份:2016
-
负责人:Joji Fujisaki
-
依托单位:
国内基金
海外基金
芍药苷靶向α-烯醇化酶治疗实验性自身免疫性脑脊髓炎的机制研究
-
批准号:82371809
-
项目类别:面上项目
-
资助金额:49.00万元
-
批准年份:2023
-
负责人:聂红
-
依托单位:
新型小分子蛋白—人肝细胞生长因子三环域(hHGFK1)抑制破骨细胞及治疗小鼠骨质疏松的疗效评估与机制研究
-
批准号:82370885
-
项目类别:面上项目
-
资助金额:49.00万元
-
批准年份:2023
-
负责人:姚晨
-
依托单位:
HER2特异性双抗原表位识别诊疗一体化探针研制与临床前诊疗效能研究
-
批准号:82372014
-
项目类别:面上项目
-
资助金额:48.00万元
-
批准年份:2023
-
负责人:魏伟军
-
依托单位: