Decreased CD56+CD16‐CD94+uNK cells in the mid‐luteal phase in women with recurrent implantation failure are associated with IL‐15 deficiency

• Published in: American journal of reproductive immunology (1989) 2023-12, Vol.90 (6), p.e13794-n/a
• Main Authors: Zhang, Xin‐Xian, Wu, Xiao‐Hua
• Format: Article
• Language: English
• Subjects: CD16 antigen; CD56 antigen; CD57 antigen; Embryo Implantation; Endometrium; Endometrium - metabolism; Female; Flow cytometry; Gene expression; human endometrium; Humans; immunology; implantation failure; in vitro fertilization; Interleukin 15; Interleukin-15 - metabolism; Luteal Phase; Natural killer cells; Peripheral blood; Reverse transcription; RNA, Messenger - genetics; RNA, Messenger - metabolism; uterine natural killer cells; uterine receptivity; Uterus - metabolism
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.13794

Problem Whether the abnormal development of uterine natural killer (uNK) cells contributes to women with recurrent implantation failure (RIF) remains unclear. Method of study We characterized the development of uNK cells and peripheral blood NK cells (pbNK) in the mid‐luteal phase in women with RIF (n = 31) and controls (n = 14) by flow cytometry. Endometrial IL‐15 mRNA expression was studied by quantitative reverse transcription‐PCR. The GSE58144 dataset was used to validate the correlation results. Results We found decreased proportions of stage 4 CD56+CD16‐CD94+ uNK cells (median: 9.56% vs. 17.78%, P .014) and increased proportions of stage 6 CD56+CD16+CD57+ uNK cells (median: 1.54% vs. 0.74%, P = .020) in the mid‐luteal endometrium of women with RIF compared to fertile women. We also found that there was no quantitative correlation between uNK cells and the corresponding pbNK cell subpopulations (P > .05). In addition, IL‐15 mRNA levels in the mid‐luteal endometrium were positively correlated with the proportion of CD56+ uNK cells (r = .392, P = .008), especially with stage 4 uNK cell populations (r = .408, P = .005). Conclusions We showed that the proportion of stage 4 uNK cells decreased in the RIF group compared to controls, and the decrease in stage 4 uNK cells correlated positively with low IL‐15 mRNA expression. We suggest that the reduced stage 4 uNK cells in women with RIF are associated with IL‐15 deficiency.