bims-reprim Biomed News
on Reproductive immunology
Issue of 2020‒10‒04
two papers selected by
Iva Filipovic
Karolinska Institutet


  1. Cell Rep. 2020 Sep 29. pii: S2211-1247(20)31193-1. [Epub ahead of print]32(13): 108204
    Benner M, Feyaerts D, García CC, Inci N, López SC, Fasse E, Shadmanfar W, van der Heijden OWH, Gorris MAJ, Joosten I, Ferwerda G, van der Molen RG.
      Well-timed interaction of correctly functioning maternal immune cells is essential to facilitate healthy placenta formation, because the uterine immune environment has to tolerate the semi-allogeneic fetus and allow adequate trophoblast invasion. Here, we assess the uterine immune signature before and during pregnancy. Extensive supervised and unsupervised flow cytometry clustering strategies not only show a general increase in immune memory throughout pregnancy but also reveal the continuous presence of B cells. Contrary to the belief that B cells are merely a consequence of uterine pathology, decidual B cells produce IL-10 and are found to be localized in clusters, together with Foxp3pos T cells. Our findings therefore suggest a role for B cells in healthy pregnancy.
    Keywords:  B cells; IL-10; decidua; endometrium; implantation; pregnancy; reproductive immunology; uterine mucosa
    DOI:  https://doi.org/10.1016/j.celrep.2020.108204
  2. Proc Natl Acad Sci U S A. 2020 Oct 01. pii: 201920037. [Epub ahead of print]
    Li WN, Hsiao KY, Wang CA, Chang N, Hsu PL, Sun CH, Wu SR, Wu MH, Tsai SJ.
      Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic regimens. Herein, we identified that vascular endothelial growth factor (VEGF)-C, a potent lymphangiogenic factor, is up-regulated in endometriotic cells and contributes to increased lymphangiogenesis. Bioinformatic analysis and molecular biological characterization revealed that VEGF-C is negatively regulated by an orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII). Further studies demonstrated that proinflammatory cytokines, via suppression of COUP-TFII level, induce VEGF-C overexpression. More importantly, we show that functional VEGF-C is transported by extracellular vesicles (EVs) to enhance the lymphangiogenic ability of lymphatic endothelial cells. Autotransplanted mouse model of endometriosis showed lenvatinib treatment abrogated the increased lymphatic vessels development in the endometriotic lesion, enlarged retroperitoneal lymph nodes, and immune cells infiltration, indicating that blocking VEGF-C signaling can reduce local chronic inflammation and concomitantly endometriosis development. Evaluation of EV-transmitted VEGF-C from patients' sera demonstrates it is a reliable noninvasive way for clinical diagnosis. Taken together, we identify the vicious cycle of inflammation, COUP-TFII, VEGF-C, and lymphangiogenesis in the endometriotic microenvironment, which opens up new horizons in understanding the pathophysiology of endometriosis. VEGF-C not only can serve as a diagnostic biomarker but also a molecular target for developing therapeutic regimens.
    Keywords:  COUP-TFII; EV; VEGF-C; biomarker; lymphangiogenesis
    DOI:  https://doi.org/10.1073/pnas.1920037117