Int J Biol Sci 2022; 18(10):4043-4052. doi:10.7150/ijbs.73616 This issue

Review

Human leukocyte antigens: the unique expression in trophoblasts and their crosstalk with local immune cells

Xin-Xiu Lin1, Ying-Ming Xie2, Si-Jia Zhao1, Chun-Yan Liu1, Gil Mor1,3, Ai-Hua Liao1✉

1. Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
2. Department of Obstetrics, Maternity and Child health care hospital Hubei, Wuhan, PR China.
3. C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, Detroit, MI, USA.

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Citation:
Lin XX, Xie YM, Zhao SJ, Liu CY, Mor G, Liao AH. Human leukocyte antigens: the unique expression in trophoblasts and their crosstalk with local immune cells. Int J Biol Sci 2022; 18(10):4043-4052. doi:10.7150/ijbs.73616. Available from https://www.ijbs.com/v18p4043.htm

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Abstract

Graphic abstract

Trophoblasts differentiate and form the placenta during pregnancy in a complex and finely orchestrated process, which is dependent on the establishment of maternal-fetal immune tolerance and the proper function of trophoblasts. Trophoblasts express HLA-C and non-classical HLA-Ib molecules (HLA-E, HLA-F, and HLA-G). Numerous studies have shown that the unique expression pattern of the HLA molecules is closely linked to the successful acceptance of allogeneic fetus by the mother during pregnancy. However, some controversies still exist concerning the exact expression and recognition patterns of HLA molecules in different trophoblast subpopulations and cell lines. Thus, we summarize three types of trophoblast subpopulations as well as the common trophoblast lineages. Then, the classification and structural characteristics of HLA molecules were elucidated. Finally, the presence of HLA-C and non-classical HLA-Ib molecules (HLA-E, HLA-F, and HLA-G) in various trophoblasts and cell lines, as well as their potential role in establishing and maintaining normal pregnancy were also discussed. Together, this review will help people comprehensively understand the complex immune interactions between maternal and fetal crosstalk during pregnancy and ultimately better understand the physiological and pathological etiologies of pregnancy.

Keywords: pregnancy, cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, HLA-C, HLA-E, HLA-F, HLA-G