bims-reprim 2022-05-01 papers

Issue of 2022–05–01
four papers selected by
Iva Filipovic, Karolinska Institutet

J Reprod Immunol. 2022 Apr 18. pii: S0165-0378(22)00156-5. [Epub ahead of print]151 103627

Cutting edge: the regulatory mechanisms of macrophage polarization and function during pregnancy.

Li-Ling Wang, Zhi-Hui Li, Huan Wang, Joanne Kwak-Kim, Ai-Hua Liao.

Macrophages are highly diverse cells and represent the major antigen-presenting cell at the maternal-fetal interface. Except for protecting the embryo with half of the paternal antigens from attack by the maternal immune system, decidua macrophages also have a critical role in implantation, trophoblast invasion, spiral artery remodeling, angiogenesis, and pathogen clearance. The classically activated (M1) and alternatively activated (M2) macrophages are the simplified classifications of macrophages, often applied to differentiate decidual macrophages. Particular phenotypes and functions of macrophages corresponding to each phase of the menstrual cycle and pregnancy are critical for establishing and maintaining pregnancy. Aberrant dynamics of decidual macrophages are associated with multiple pregnancy complications, such as recurrent pregnancy loss, preeclampsia, and preterm birth. Although various factors are related to decidual macrophage polarization, including cytokines, growth factors, hormones, and transcription factors, the potential regulatory mechanisms underlying decidual macrophage polarization are still unclear. Therefore, a thorough understanding of macrophage function and regulatory mechanism during pregnancy is critical to clarify the pathogenesis of pregnancy complications. In this review, we first describe an overview of the origin, phenotype, and function of macrophages in the uterus. Secondly, we propose emerging concepts explaining how macrophage polarization and functions are regulated, including immunometabolism, epigenetics, immune checkpoint, and microorganisms. Finally, we review the potential relationship among these novel factors in regulating the function of the immune system.

Keywords: Epigenetics; Immune checkpoint; Immunometabolism; Macrophage; Microorganisms; Pregnancy

DOI: https://doi.org/10.1016/j.jri.2022.103627

Int Rev Cell Mol Biol. 2022 ;pii: S1937-6448(22)00032-6. [Epub ahead of print]367 183-208

Endometrial macrophages in health and disease.

Erin Brown, Rocío Martínez-Aguilar, Jacqueline A Maybin, Douglas A Gibson.

Macrophages are present in the endometrium throughout the menstrual cycle and are most abundant during menstruation. Endometrial macrophages contribute to tissue remodeling during establishment of pregnancy and are thought to play key roles in mediating tissue breakdown and repair during menstruation. Despite these important roles, the phenotype and function of endometrial macrophages remains poorly understood. In this review, we summarize approaches used to characterize endometrial macrophage phenotype, current understanding of the functional role of macrophages in normal endometrial physiology as well as the putative contribution of macrophage dysfunction to women's reproductive health disorders.

Keywords: Abnormal uterine bleeding; Endometriosis; Endometrium; Heavy menstrual bleeding; Macrophage; Menstruation; Uterus

DOI: https://doi.org/10.1016/bs.ircmb.2022.03.011

Semin Immunopathol. 2022 Apr 29.

Tissue-resident immunity in the female and male reproductive tract.

Dennis Yüzen, Petra Clara Arck, Kristin Thiele.

The conception of how the immune system is organized has been significantly challenged over the last years. It became evident that not all lymphocytes are mobile and recirculate through secondary lymphoid organs. Instead, subsets of immune cells continuously reside in tissues until being reactivated, e.g., by a recurring pathogen or other stimuli. Consequently, the concept of tissue-resident immunity has emerged, and substantial evidence is now available to support its pivotal function in maintaining tissue homeostasis, sensing challenges and providing antimicrobial protection. Surprisingly, insights on tissue-resident immunity in the barrier tissues of the female reproductive tract are sparse and only slowly emerging. The need for protection from vaginal and amniotic infections, the uniqueness of periodic tissue shedding and renewal of the endometrial barrier tissue, and the demand for a tailored decidual immune adaptation during pregnancy highlight that tissue-resident immunity may play a crucial role in distinct compartments of the female reproductive tract. This review accentuates the characteristics of tissue-resident immune cells in the vagina, endometrium, and the decidua during pregnancy and discusses their functional role in modulating the risk for infertility, pregnancy complications, infections, or cancer. We here also review data published to date on tissue-resident immunity in the male reproductive organs, which is still a largely uncharted territory.

Keywords: Cancer; Decidua; Endometrium; FRT; Immune memory; Pregnancy; Testis; Tissue-resident; Uterus; Vagina

DOI: https://doi.org/10.1007/s00281-022-00934-8

JCI Insight. 2022 Apr 26. pii: e155482. [Epub ahead of print]

Placental dysfunction influences fetal monocyte subpopulation gene expression in preterm birth.

Abhineet M Sharma, Robert Birkett, Erika T Lin, Linda M Ernst, William A Grobman, Suchitra Swaminathan, Hiam Abdala-Valencia, Alexander V Misharin, Elizabeth T Bartom, Karen K Mestan.

The placenta is the primary organ for immune regulation, nutrient delivery, gas exchange, protection against environmental toxins, and physiologic perturbations during pregnancy. Placental inflammation and vascular dysfunction during pregnancy are associated with a growing list of prematurity-related complications. The goal of this study was to identify differences in gene expression profiles in fetal monocytes - cells that persist and differentiate postnatally - according to distinct placental histologic domains. Here, by using bulk RNA sequencing (RNA-Seq), we report that placental lesions are associated with gene expression changes in fetal monocyte subsets. Specifically, we found that fetal monocytes exposed to acute placental inflammation upregulate biological processes related to monocyte activation, monocyte chemotaxis, and platelet function while monocytes exposed to maternal vascular malperfusion lesions downregulate these processes. Additionally, we show that intermediate monocytes might be a source of mitogens, such as HBEGF, NRG1, and VEGFA, implicated in different outcomes related to prematurity. This is the first study to show that placental lesions are associated with unique changes in fetal monocytes and monocyte subsets. As fetal monocytes persist and differentiate into various phagocytic cells following birth, our study may provide insight into morbidity related to prematurity and ultimately potential therapeutic targets.

Keywords: Adaptive immunity; Chemokines; Monocytes; Reproductive Biology; Vascular Biology

DOI: https://doi.org/10.1172/jci.insight.155482