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IFN-? induces aberrant CD49b? NK cell recruitment through regulating CX3CL1: a novel mechanism by which IFN-? provokes pregnancy failure.


ABSTRACT: Interferon-? (IFN-?), a pleiotropic lymphokine, has important regulatory effects on many cell types. Although IFN-? is essential for the initiation of uterine vascular modifications and maintenance of decidual integrity, IFN-? administration can also cause pregnancy failure in many species. However, little is known about the effector mechanisms involved. In this study, using an IFN-?-induced abortion mouse model, we reported that no Dolichos biflorus agglutinin lectin-positive uterine natural killer (uNK) cells were observed in the uteri from IFN-?-induced abortion mice. By contrast, the percentage of CD3(-)CD49b(+) NK cells in the uterus and blood from a foetal resorption group was significantly higher than that of the control group. Similarly, significantly upregulated expression of CD49b (a pan-NK cell marker), CX3CL1 and CX3CR1 (CX3CL1 receptor) was detected in the uteri of IFN-?-induced abortion mice. Using isolated uterine stromal cells, we showed that upregulated expression of CX3CL1 by IFN-? was dependent on a Janus family kinase 2-signal transducers and activators of transcription 1 (JAK2-STAT1) pathway. We further demonstrated the chemotactic activity of CX3CL1 in uterine stromal cell conditioned medium on primary splenic NK cells. Finally, we observed increased recruitment of CD49b(+) NK cells into the endometrium after exogenous CX3CL1 administration. Collectively, our findings indicate that IFN-? can significantly increase uterine CX3CL1 expression via activation of the JAK2-STAT1 pathway, thus inducing CD49b(+) NK cell uterine homing, and eventually provoke foetal loss. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-? on pregnancy with the aberrant regulation of CX3CL1 and CD49b(+) NK cells.

SUBMITTER: Li ZY 

PROVIDER: S-EPMC4260728 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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IFN-γ induces aberrant CD49b⁺ NK cell recruitment through regulating CX3CL1: a novel mechanism by which IFN-γ provokes pregnancy failure.

Li Z-Y ZY   Chao H-H HH   Liu H-Y HY   Song Z-H ZH   Li L-L LL   Zhang Y-J YJ   Yang Y Y   Peng J-P JP  

Cell death & disease 20141106


Interferon-γ (IFN-γ), a pleiotropic lymphokine, has important regulatory effects on many cell types. Although IFN-γ is essential for the initiation of uterine vascular modifications and maintenance of decidual integrity, IFN-γ administration can also cause pregnancy failure in many species. However, little is known about the effector mechanisms involved. In this study, using an IFN-γ-induced abortion mouse model, we reported that no Dolichos biflorus agglutinin lectin-positive uterine natural ki  ...[more]

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2021-01-08 | GSE144859 | GEO