CD8aa+ Cells and Ovarian Functions

CD8aa 细胞和卵巢功能

• 批准号: 7858175
• 负责人: YAHUAN LOU
• 金额: $ 23.22万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7858175
• 关键词: Active Immunization; Antibodies; Antral; Biological Assay; Biology; CD8B1 gene; Cells; Chemotactic Factors; Chemotaxis; Coculture Techniques; Development; Estrus; Female; Fertility; Flow Cytometry; Functional disorder; Gene Expression; Homing; Hormones; Human Chorionic Gonadotropin; Immune; Immune system; Immunization; Immunology; In Vitro; Inbred BALB C Mice; Infertility; Infiltration; Injection of therapeutic agent; Investigation; Knockout Mice; Luteinization; Modeling; Mus; Nude Mice; Ovarian; Ovary; Ovulation; Ovulation Induction; Periodicity; Phenotype; Population; Recombinants; Recruitment Activity; Regulation; Research; Research Personnel; Role; System; Testing; Theca folliculi structure; Thymectomy; Thymus Gland; Time; base; cell determination; chemokine; design; experience; hormone regulation; human CCL25 protein; novel; programs; receptor; reconstitution; thymocyte

DESCRIPTION (provided by applicant): In this application, we proposed to investigate how a novel ovarian CD8aa+ cell population participates in important ovarian functions such as ovulation. Involvement of the immune system in ovarian functions has been recognized. The critical role of the thymus in ovarian functions is well known. Thus, athymic nude female mice are infertile, and thymectomy leads to ovarian dysfunctions. However, it remains unclear how the thymus participates in ovarian functions. We have identified a novel CD8aa+ population in the internal of antral follicles and their dramatic influx into the ovulating follicles during hCG-induced ovulation. This novel CD8aa+ cells probably originate from thymus and involved in important ovarian functions such as ovulation. Thus, transfer of syngeneic thymocytes, which contain several CD8aa+ cell populations, into the female nude mice restored their ovulatory ability. We next identified ovarian expression of chemokine TECK (thymus expressed chemokine) to be critical for the homing and influx of CD8aa+ cells into the ovary during ovulation. Thus, eliciting anti-TECK antibody by active immunization in the female BALB/c mice led to not only diminishment of the ovarian CD8aa+ cells but also infertility in the immunized mice. Based on the above results, we hypothesize a novel relationship between the thymus and the ovarian functions: 1) the novel CD8aa+ cells are originated from the thymus and recruited into the ovary by ovarian TECK, which is under hormonal regulation, and 2) the CD8aa+ cells are critical for ovulation/luteinization. This is intended to test out hypothesis by 1) determination of lineage and phenotype of ovarian CD8aa+, 2) identification of ovarian function that the ovarian CD8aa+ cells participate in, and 3) identification of TECK- expressing ovarian cells and determination of hormonal regulation of TECK expression in the ovary.

描述（由申请人提供）：在本申请中，我们提议研究新型卵巢CD8aa+细胞群如何参与重要的卵巢功能，例如排卵。免疫系统参与卵巢功能已被认识到。胸腺在卵巢功能中的关键作用是众所周知的。因此，无胸腺雌性裸鼠不育，胸腺切除会导致卵巢功能障碍。然而，目前尚不清楚胸腺如何参与卵巢功能。我们在窦卵泡内部发现了一种新的 CD8aa+ 群体，并且在 hCG 诱导排卵期间它们大量流入排卵卵泡。这种新型 CD8aa+ 细胞可能源自胸腺，参与重要的卵巢功能，例如排卵。因此，将含有多个CD8aa+细胞群的同基因胸腺细胞转移到雌性裸鼠体内恢复了它们的排卵能力。接下来，我们发现趋化因子 TECK（胸腺表达趋化因子）的卵巢表达对于排卵期间 CD8aa+ 细胞归巢并流入卵巢至关重要。因此，通过主动免疫在雌性 BALB/c 小鼠中引发抗 TECK 抗体不仅导致卵巢 CD8aa+ 细胞减少，而且导致免疫小鼠不育。基于上述结果，我们假设胸腺和卵巢功能之间存在一种新的关系：1）新的CD8aa+细胞起源于胸腺，并通过受激素调节的卵巢TECK招募到卵巢；2）CD8aa+细胞对于排卵/黄体化至关重要。目的是通过 1) 确定卵巢 CD8aa+ 的谱系和表型，2) 鉴定卵巢 CD8aa+ 细胞参与的卵巢功能，以及 3) 鉴定表达 TECK 的卵巢细胞并确定卵巢中 TECK 表达的激素调节来检验假设。

项目成果

Requirement of brain interleukin33 for aquaporin4 expression in astrocytes and glymphatic drainage of abnormal tau.

• DOI: 10.1038/s41380-020-00992-0
• 发表时间: 2021-10
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Wu J;Carlock C;Shim J;Moreno-Gonzalez I;Glass W 2nd;Ross A;Barichello T;Quevedo J;Lou Y
• 通讯作者: Lou Y

IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration.

• DOI: 10.4049/jimmunol.1402503
• 发表时间: 2015-03-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Wu J;Carlock C;Zhou C;Nakae S;Hicks J;Adams HP;Lou Y
• 通讯作者: Lou Y