Open AccessCytochrome P450 26A1 modulates natural killer cells in mouse early pregnancy
Author(s) -
Meng ChaoYang,
Li ZhongYin,
Fang WenNing,
Song ZhiHui,
Yang DanDan,
Li DanDan,
Yang Ying,
Peng JingPian
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13013
Subject(s) - biology , gene knockdown , microbiology and biotechnology , natural killer cell , andrology , cytotoxic t cell , cell culture , in vitro , genetics , medicine
Cytochrome P450 26A1 ( CYP 26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri‐implantation. Inhibiting the function or expression of CYP 26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP 26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR 3.1‐cyp26a1 plasmid immunization mouse model and a Cyp26a1‐ MO ( Cyp26a1 ‐specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin ( DBA ) lectin‐positive uterine natural killer ( uNK ) cells was reduced in pCR 3.1‐cyp26a1 plasmid immunized and Cyp26a1‐ MO ‐treated mice. In contrast, the percentage of CD 3 − CD 49b + NK cells in the uteri from the treatment group was significantly higher than that of the control group in both models. Similarly, significantly up‐regulated expression of CD 49b (a pan‐ NK cell marker), interferon gamma, CCL 2, CCR 2 ( CCL 2 receptor) and CCL 3 were detected in the uteri of pCR 3.1‐cyp26a1‐ and Cyp26a1‐ MO ‐treated mice. Transcriptome analysis suggested that CYP 26A1 might regulate NK cells through chemokines. In conclusion, the present data suggest that silencing CYP 26A1 expression/function can decrease the number of uNK cells and significantly increase the percentage of CD 3 − CD 49b + NK cells in the uteri of pregnant mice. These findings provide a new line of evidence correlating the deleterious effects of blocking CYP 26A1 in pregnancy with the aberrant regulation of NK cells in the uterus.