Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube

PD-1免疫检查点在卵巢和输卵管中的表达及T细胞调控作用

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作者:Joshua Johnson, So-Youn Kim, Peter Ka Sam, Rengasamy Asokan, Evelyn Llerena Cari, Elise S Bales, Thanh-Ha Luu, Lauren Perez, Amanda N Kallen, Liesl Nel-Themaat, Alex J Polotsky, Miriam D Post, David J Orlicky, Kimberly R Jordan, Benjamin G Bitler

Conclusion

The detection of PD-1 checkpoint proteins in the human ovary and fallopian tube suggests that the pathway is involved in immunomodulation during folliculogenesis, the window of ovulation, and subsequent egg and embryo immune-privilege. Immunomodulatory action of receptor and ligands in HFF exosomes is suggestive of an acute checkpoint role during ovulation. This is the first study in the role of PD-1 checkpoint proteins in human tubo-ovarian specimens and the first examination of its potential regulatory action in the contexts of normal and assisted reproduction.

Results

We show that membrane bound and soluble variants of PD-1 and ligands are expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were present in HFF at bioactive levels that control T cell PD-1 activation and IFNγ production; full-length checkpoint proteins were found to be highly enriched in HFF exosome fractions.

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