bims-reprim Biomed News
on Reproductive immunology
Issue of 2021–06–27
six papers selected by
Iva Filipovic, Karolinska Institutet
  1. Distinct populations of antigen specific tissue resident CD8 T cells in human cervix mucosa.
  2. High fat diet alters male seminal plasma composition to impair female immune adaptation for pregnancy in mice.
  3. Circulating and Endometrial Regulatory T Cell and Related Populations in Endometriosis and Infertility: Endometriosis Is Associated with Blunting of Endometrial Cyclical Effects and Reduced Proportions in Moderate-Severe Disease.
  4. Pregnancy Induces an Immunological Memory Characterized by Maternal Immune Alterations Through Specific Genes Methylation.
  5. The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.
  6. The emerging role of group 3 innate lymphoid cells in the neonate: interaction with the maternal and neonatal microbiome.
  1. JCI Insight. 2021 Jun 22. pii: 149950. [Epub ahead of print]
    Distinct populations of antigen specific tissue resident CD8 T cells in human cervix mucosa.
    Tao Peng, Khamsone Phasouk, Emily Bossard, Alexis Klock, Lei Jin, Kerry J Laing, Christine Johnston, Noel A Williams, Julie L Czartoski, Dana Varon, Annalyssa N Long, Jason H Bielas, Thomas M Snyder, Harlan Robins, David M Koelle, M Juliana McElrath, Anna Wald, Lawrence Corey, Jia Zhu.
      The ectocervix is part of the lower female reproductive tract (FRT), which is susceptible to sexually transmitted infections (STI). Comprehensive knowledge of the phenotypes and T cell receptor (TCR) repertoire of tissue resident memory T cells (TRM) in human FRT is lacking. We have taken single-cell RNA sequencing approaches to simultaneously define gene expression and TCR clonotypes of the human ectocervix. There are significantly more CD8 than CD4 T cells. Unsupervised clustering and trajectory analysis identify distinct populations of CD8 T cells with IFNGhiGZMBlowCD69hiCD103low or IFNGlowGZMBhiCD69medCD103hi phenotypes. Little overlap was seen between their TCR repertoires. Immunofluorescent staining shows that CD103+ CD8 TRM cells preferentially localize in epithelium while CD69+ CD8 TRM distribute evenly in epithelium and stroma. Ex vivo assays indicate up to 14% of cervical CD8 TRM clonotypes are HSV-2 reactive in HSV-2-seropositive persons, reflecting physiologically relevant localization. Our studies identify subgroups of CD8 TRM in the human ectocervix that exhibit distinct expression of antiviral defense and tissue residency markers, anatomic locations, and TCR repertoires that target anatomically relevant viral antigens. Optimization of the location, number, and function of FRT TRM is an important approach for improving host defenses to STI.
    Keywords:  Adaptive immunity; Immunology; T cells; Virology
    DOI:  https://doi.org/10.1172/jci.insight.149950
  2. Endocrinology. 2021 Jun 25. pii: bqab123. [Epub ahead of print]
    High fat diet alters male seminal plasma composition to impair female immune adaptation for pregnancy in mice.
    John E Schjenken, Lachlan M Moldenhauer, David J Sharkey, Hon Yeung Chan, Peck Y Chin, Tod Fullston, Nicole O McPherson, Sarah A Robertson.
      Paternal experiences and exposures prior to conception can influence fetal development and offspring phenotype. The composition of seminal plasma contributes to paternal programming effects, through modulating the female reproductive tract immune response after mating. To investigate whether paternal obesity affects seminal plasma immune-regulatory activity, C57Bl/6 male mice were fed an obesogenic high fat diet (HFD) or control diet (CD) for 14 weeks. While HFD consumption caused only minor changes to parameters of sperm quality, the volume of seminal vesicle fluid secretions was increased by 65%, and the concentrations and total content of immune-regulatory TGFB isoforms were decreased by 75-80% and 43-55% respectively. Mating with BALB/c females revealed differences in the strength and properties of the post-mating immune response elicited. Transcriptional analysis showed >300 inflammatory genes were similarly regulated in the uterine endometrium by mating independently of paternal diet, but 13 were dysregulated by HFD-fed compared to CD-fed males. Seminal vesicle fluid factors reduced in HFD-fed males, including TGFB1, IL10, and TNF, were amongst the predicted upstream regulators of differentially regulated genes. Additionally, the T cell response induced by mating with CD-fed males was blunted after mating with HFD-fed males, with 27% fewer CD4 + T cells, 26% fewer FOXP3 +CD4 + regulatory T cells (Treg) cells, and 19% fewer CTLA4 + Treg cells, particularly within the NRP1 + thymic Treg cell population. These findings demonstrate that an obesogenic high fat diet alters the composition of seminal vesicle fluid and impairs seminal plasma capacity to elicit a favorable pro-tolerogenic immune response in females at conception.
    Keywords:  Cytokine; Mouse; Obesity; Seminal fluid; Treg cell
    DOI:  https://doi.org/10.1210/endocr/bqab123
  3. Reprod Sci. 2021 Jun 23.
    Circulating and Endometrial Regulatory T Cell and Related Populations in Endometriosis and Infertility: Endometriosis Is Associated with Blunting of Endometrial Cyclical Effects and Reduced Proportions in Moderate-Severe Disease.
    A J Hey-Cunningham, A Riaz, P D Fromm, F Kupresanin, R Markham, H M McGuire.
      Evidence to date supports regulatory T cell (Treg) alterations in endometriosis; however, the relationship remains unclear, and Tregs have not previously been investigated with respect to infertility in endometriosis. This prospective cross-sectional cohort study details circulating and endometrial tissue-specific disturbances in Tregs and broader gated populations in women of reproductive age with and without endometriosis (n = 57 and 29, respectively) using flow cytometry and immunohistochemistry. Participants were characterised by menstrual cycle phase, r-ASRM endometriosis disease stage and fertility status.In the endometrium of women with endometriosis, endometrial Tregs and CD4+ lymphocyte proportions did not change between the proliferative and secretory phases, while in women without the disease, they significantly decreased (p = 0.045 and p = 0.039, respectively). In women with endometriosis, endometrial Tregs were lower than in women without endometriosis overall (p = 0.050 as a proportion of all CD45+ immune cells). We have shown for the first time that proportions of CD4+ lymphocytes (p = 0.021), overall lymphocytes (p = 0.034) and non-granulocytes (p = 0.027) were significantly decreased in the endometrium of women with moderate-severe (r-ASRM stages III and IV) compared to minimal-mild (r-ASRM stages I and II) endometriosis. During the secretory phase, circulating Treg proportions were significantly increased in infertile compared to fertile women (p = 0.049). This study confirms differences in endometrial Tregs in women with endometriosis, with blunting of normal menstrual cyclical variations, reduced proportions during the proliferative phase and disease stage-specific relationships.
    Keywords:  Blood; Endometriosis; Endometrium; Infertility; Menstrual cycle; Regulatory T cells
    DOI:  https://doi.org/10.1007/s43032-021-00658-4
  4. Front Immunol. 2021 ;12 686676
    Pregnancy Induces an Immunological Memory Characterized by Maternal Immune Alterations Through Specific Genes Methylation.
    Xiaobo Huang, Liling Wang, Sijia Zhao, Hong Liu, Si Chen, Li Wu, Liping Liu, Jiahui Ding, Hengwen Yang, Anthony Maxwell, Zhinan Yin, Gil Mor, Aihua Liao.
      During pregnancy, the maternal immune system undergoes major adaptive modifications that are necessary for the acceptance and protection of the fetus. It has been postulated that these modifications are temporary and limited to the time of pregnancy. Growing evidence suggests that pregnancy has a long-term impact on maternal health, especially among women with pregnancy complications, such as preeclampsia (PE). In addition, the presence of multiple immunological-associated changes in women that remain long after delivery has been reported. To explain these long-term modifications, we hypothesized that pregnancy induces long-term immunological memory with effects on maternal well-being. To test this hypothesis, we evaluated the immunological phenotype of circulating immune cells in women at least 1 year after a normal pregnancy and after pregnancy complicated by PE. Using multiparameter flow cytometry (FCM) and whole-genome bisulfite sequencing (WGBS), we demonstrate that pregnancy has a long-term effect on the maternal immune cell populations and that this effect differs between normal pregnancy and pregnancy complicated by PE; furthermore, these modifications are due to changes in the maternal methylation status of genes that are associated with T cell and NK cell differentiation and function. We propose the existence of an "immunological memory of pregnancy (IMOP)" as an evolutionary advantage for the success of future pregnancies and the proper adaptation to the microchimeric status established during pregnancy. Our findings demonstrate that the type of immune cell populations modified during pregnancy may have an impact on subsequent pregnancy and future maternal health.
    Keywords:  epigenetic; immune cells; immunological memory; preeclampsia; pregnancy
    DOI:  https://doi.org/10.3389/fimmu.2021.686676
  5. Front Immunol. 2021 ;12 689019
    The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.
    Pengfei Chen, Liying Zhou, Jiying Chen, Ying Lu, Chaoxia Cao, Shuangli Lv, Zhihong Wei, Liping Wang, Jiao Chen, Xinglin Hu, Zijing Wu, Xiaohua Zhou, Danna Su, Xuefeng Deng, Changchun Zeng, Huiyun Wang, Zuhui Pu, Ruiying Diao, Lisha Mou.
      Recurrent pregnancy loss (RPL) is a common fertility problem that affects 1%-2% of couples all over the world. Despite exciting discoveries regarding the important roles of the decidual natural killer cell (dNK) and regulatory T cell in pregnancy, the immune heterogeneity in patients with unexplained recurrent pregnancy loss (URPL) remains elusive. Here, we profiled the transcriptomes of 13,953 CD45+ cells from three normal and three URPL deciduas. Based on our data, the cellular composition revealed three major populations of immune cells including dNK cell, T cell, and macrophage, and four minor populations including monocytes, dendritic cell (DC), mast cell, and B cell. Especially, we identified a subpopulation of CSF1+ CD59+ KIRs-expressing dNK cells in normal deciduas, while the proportion of this subpopulation was decreased in URPL deciduas. We also identified a small subpopulation of activated dDCs that were accumulated mainly in URPL deciduas. Furthermore, our data revealed that in decidua at early pregnancy, CD8+ T cells exhibited cytotoxic properties. The decidual macrophages expressed high levels of both M1 and M2 feature genes, which made them unique to the conventional M1/M2 classification. Our single-cell data revealed the immune heterogeneity in decidua and the potentially pathogenic immune variations in URPL.
    Keywords:  human decidua; immune heterogeneity; scRNA decidual nature killer cell; single-cell RNA sequencing; the immune atlas; unexplained recurrent pregnancy loss
    DOI:  https://doi.org/10.3389/fimmu.2021.689019
  6. Oxf Open Immunol. 2021 ;2(1): iqab009
    The emerging role of group 3 innate lymphoid cells in the neonate: interaction with the maternal and neonatal microbiome.
    Julie Mirpuri.
      Innate lymphoid cells (ILCs) are critical for host defense and are notably important in the context of the newborn when adaptive immunity is immature. There is an increasing evidence that development and function of group 3 ILCs (ILC3) can be modulated by the maternal and neonatal microbiome and is involved in neonatal disease pathogenesis. In this review, we explore the evidence that supports a critical role for ILC3 in resistance to infection and disease pathogenesis in the newborn, with a focus on microbial factors that modulate ILC3 function. We then briefly explore opportunities for research that are focused on the fetus and newborn.
    Keywords:  innate lymphoid cells; lc3; maternal; microbiome; neonatal
    DOI:  https://doi.org/10.1093/oxfimm/iqab009
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