Ovarian Dendritic Cells Act as a Double-Edged Pro-Ovulatory and Anti-Inflammatory Sword

被引:38
作者
Cohen-Fredarow, Adva [1 ]
Tadmor, Ari [1 ]
Raz, Tal [2 ]
Meterani, Naama [1 ]
Addadi, Yoseph [1 ,3 ]
Nevo, Nava [1 ]
Solomonov, Inna [1 ]
Sagi, Irit [1 ]
Mor, Gil [4 ]
Neeman, Michal [1 ]
Dekel, Nava [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] Hebrew Univ Jerusalem, Koret Sch Vet Med, IL-76100 Rehovot, Israel
[3] B Nano Ltd, IL-76326 Rehovot, Israel
[4] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06510 USA
基金
以色列科学基金会; 欧洲研究理事会;
关键词
TUMOR-NECROSIS-FACTOR; MESSENGER-RIBONUCLEIC-ACID; IN-VIVO DEPLETION; RAT OVARY; FOLLICULAR DEVELOPMENT; LYMPHATIC VASCULATURE; REGULATED EXPRESSION; EMBRYO IMPLANTATION; SIGNALING PATHWAYS; STIMULATED GENE-6;
D O I
10.1210/me.2013-1400
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ovulation and inflammation share common attributes, including immune cell invasion into the ovary. The present study aims at deciphering the role of dendritic cells (DCs) in ovulation and corpus luteum formation. Using a CD11c-EYFP transgenic mouse model, ovarian transplantation experiments, and fluorescence-activated cell sorting analyses, we demonstrate that CD11c-positive, F4/80-negative cells, representing DCs, are recruited to the ovary under gonadotropin regulation. By conditional ablation of these cells in CD11c-DTR transgenic mice, we revealed that they are essential for expansion of the cumulus-oocyte complex, release of the ovum from the ovarian follicle, formation of a functional corpus luteum, and enhanced lymphangiogenesis. These experiments were complemented by allogeneic DC transplantation after conditional ablation of CD11c-positive cells that rescued ovulation. The pro-ovulatory effects of these cells were mediated by up-regulation of ovulation-essential genes. Interestingly, we detected a remarkable anti-inflammatory capacity of ovarian DCs, which seemingly serves to restrict the ovulatory-associated inflammation. In addition to discovering the role of DCs in ovulation, this study implies the extended capabilities of these cells, beyond their classic immunologic role, which is relevant also to other biological systems.
引用
收藏
页码:1039 / 1054
页数:16
相关论文
共 83 条
[1]   THE INVOLVEMENT OF PLATELET ACTIVATING FACTOR IN OVULATION [J].
ABISOGUN, AO ;
BRAQUET, P ;
TSAFRIRI, A .
SCIENCE, 1989, 243 (4889) :381-383
[2]   THE POTENTIAL RELEVANCE OF CYTOKINES TO OVARIAN PHYSIOLOGY [J].
ADASHI, EY .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1992, 43 (05) :439-444
[3]   Transactivation of the Epidermal Growth Factor Receptor Is Involved in the Lutropin Receptor-Mediated Down-Regulation of Ovarian Aromatase Expression in Vivo [J].
Andric, Nebojsa ;
Thomas, Mika ;
Ascoli, Mario .
MOLECULAR ENDOCRINOLOGY, 2010, 24 (03) :552-560
[4]  
Angeli Veronique, 2006, Lymphatic Research and Biology, V4, P217, DOI 10.1089/lrb.2006.4406
[5]   Tumour necrosis factor and cancer [J].
Balkwill, Frances .
NATURE REVIEWS CANCER, 2009, 9 (05) :361-371
[6]  
Bar-On L, 2010, METHODS MOL BIOL, V595, P429, DOI 10.1007/978-1-60761-421-0_28
[7]   Dendritic Cells Promote Pancreatic Viability in Mice With Acute Pancreatitis [J].
Bedrosian, Andrea S. ;
Nguyen, Andrew H. ;
Hackman, Michael ;
Connolly, Michael K. ;
Malhotra, Ashim ;
Ibrahim, Junaid ;
Cieza-Rubio, Napoleon E. ;
Henning, Justin R. ;
Barilla, Rocky ;
Rehman, Adeel ;
Pachter, H. Leon ;
Medina-Zea, Marco V. ;
Cohen, Steven M. ;
Frey, Alan B. ;
Acehan, Devrim ;
Miller, George .
GASTROENTEROLOGY, 2011, 141 (05) :1915-U508
[8]   Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity [J].
Bennett, CL ;
van Rijn, E ;
Jung, S ;
Inaba, K ;
Steinman, RM ;
Kapsenberg, ML ;
Clausen, BE .
JOURNAL OF CELL BIOLOGY, 2005, 169 (04) :569-576
[9]   DC ablation in mice: promises, pitfalls, and challenges [J].
Bennett, Clare L. ;
Clausen, Bjoern E. .
TRENDS IN IMMUNOLOGY, 2007, 28 (12) :525-531
[10]   Reduction of ovulation rate in the rat by administration of a neutrophil-depleting monoclonal antibody [J].
Brannstrom, M ;
Bonello, N ;
Norman, RJ ;
Robertson, SA .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 1995, 29 (03) :265-270