title: IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis.
abstract: Endometriosis (EMS) is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissues. It has been reported that human endometrial stromal cells (ESCs) express interleukin (IL)15. The aim of our study was to elucidate whether or not IL15 regulates the cross talk between ESCs and natural killer (NK) cells in the endometriotic milieu and, if so, how this regulation occurs. The ESC behaviors in vitro were verified by Cell Counting Kit-8 (CCK-8), Annexin/PI, and Matrigel invasion assays, respectively. To imitate the local immune microenvironment, the co-culture system between ESCs and NK cells was constructed. The effect of IL15 on NK cells in the co-culture unit was investigated by flow cytometry (FCM). In this study, we found that ectopic endometrium from patients with EMS highly expressed IL15. Rapamycin, an autophagy inducer, decreased the level of IL15 receptors (i.e. IL15Rα and IL2Rβ). IL15 inhibits apoptosis and promotes the invasiveness, viability, and proliferation of ESCs. Meanwhile, a co-culture with ESCs led to a decrease in CD16 on NK cells. In the co-culture system, IL15 treatment downregulated the levels of Granzyme B and IFN-γ in CD16(+)NK cells, NKG2D in CD56(dim)CD16(-)NK cells, and NKP44 in CD56(bright)CD16(-)NK cells. On the one hand, these results indicated that IL15 derived from ESCs directly stimulates the growth and invasion of ESCs. On the other hand, IL15 may help the immune escape of ESCs by suppressing the cytotoxic activity of NK cells in the ectopic milieu, thereby facilitating the progression of EMS.
authors.affiliation: Department of GynecologyChangzhou NO.2 People's Hospital, affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Department of GynecologyChangzhou NO.2 People's Hospital, affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China.
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Sun
authors.affiliation: Department of GynecologyChangzhou NO.2 People's Hospital, affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China.
authors.forename: Zhong-Fang
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Department of GynecologyChangzhou NO.2 People's Hospital, affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China mqli@fudan.edu.cn rena63@live.cn.
authors.forename: Ru-Xia
authors.initials: RX
authors.lastname: Shi
authors.affiliation: Department of GynecologyChangzhou NO.2 People's Hospital, affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Shang
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wei
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Chang
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRDFudan University, Shanghai, People's Republic of China Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai, People's Republic of China mqli@fudan.edu.cn rena63@live.cn.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: C569274:IL15 protein, human; D019409:Interleukin-15