Search

The incidence of allergic diseases has been rising over the past decades, and this troubling trend coincides with environmental changes such as shifts in diet and increased antibiotic use, both of which can impact our immune system. Allergic reactions occur when the immune system overreacts to normally harmless substances, and it is known that regulatory T cells (Tregs) play a major role in immune system suppression and the generation of tolerance. However, new research suggests that Tregs can malfunction in environments that promote allergies. This review delves into Treg function, and how environmental factors can influence their ability to maintain immune homeostasis. Specifically, we explore the origins of Treg cells, as well as the mechanisms used for suppression of inflammation and tissue healing, with a concentration on food allergies, atopic dermatitis and asthma. Understanding Treg function in the context of a changing environment is crucial for developing new strategies to prevent and treat allergies. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic disease among children, with more than 300 million cases worldwide. Over the past several decades, asthma incidence has grown, and epidemiological studies identify the modernized lifestyle as playing a strong contributing role in this phenomenon. In particular, lifestyle factors that modify the maternal gut microbiome during pregnancy, or the infant microbiome in early life, can act as developmental programming events which determine health or disease susceptibility later in life. Microbial colonization of the gut begins at birth, and factors such as delivery mode, breastfeeding, diet, antibiotic use, and exposure to environmental bacteria influence the development of the infant microbiome. Colonization of the gut microbiome is crucial for proper immune system development and disruptions to this process can predispose a child to asthma development. Here, we describe the importance of early‐life events for shaping immune responses along the gut‐lung axis and why they may provide a window of opportunity for asthma prevention. [ABSTRACT FROM AUTHOR]

Pregnancy is a finely tuned process, with the health and well‐being of the developing fetus determined by the metabolic status and dietary intake of the mother. The maternal gut microbiome is remodeled during pregnancy, and this, coupled with the maternal nutrient intake during gestation shapes the production of metabolites that can cross the placenta and affect fetal development. As posited by the Developmental Origins of Health and Disease Hypothesis, such environmental influences can have major effects on the developing organ systems. When occurring at particularly sensitive gestational time points, these developmental programming events can have long lasting effects on offspring adaptation to the postnatal environment, and major health implications later in life. This review will summarize current knowledge on how pregnancy and maternal dietary intake intrinsically and extrinsically modify maternal gut microbiota composition and metabolite production. Further, we will assess how these factors shape the fetal landscape and ultimately contribute to offspring health. DOHaD, fetal development, metabolites, microbiome, nutrition, pregnancy, short‐chain fatty acids [ABSTRACT FROM AUTHOR]

Antibiotic use during pregnancy is associated with increased asthma risk in children. Since approximately 25% of women use antibiotics during pregnancy, it is important to identify the pathways involved in this phenomenon. We investigate how mother‐to‐offspring transfer of antibiotic‐induced gut microbial dysbiosis influences immune system development along the gut–lung axis. Using a mouse model of maternal antibiotic exposure during pregnancy, we immunophenotyped offspring in early life and after asthma induction. In early life, prenatal‐antibiotic exposed offspring exhibited gut microbial dysbiosis, intestinal inflammation (increased fecal lipocalin‐2 and IgA), and dysregulated intestinal ILC3 subtypes. Intestinal barrier dysfunction in the offspring was indicated by a FITC‐dextran intestinal permeability assay and circulating lipopolysaccharide. This was accompanied by increased T‐helper (Th)17 cell percentages in the offspring's blood and lungs in both early life and after allergy induction. Lung tissue additionally showed increased percentages of RORγt T‐regulatory (Treg) cells at both time points. Our investigation of the gut–lung axis identifies early‐life gut dysbiosis, intestinal inflammation, and barrier dysfunction as a possible developmental programming event promoting increased expression of RORγt in blood and lung CD4+ T cells that may contribute to increased asthma risk. [ABSTRACT FROM AUTHOR]

Problem: Proper placental development is pivotal to ensure healthy pregnancy outcomes. Among the multiple cellular mechanisms involved in the orchestration of this process, little is known on the role of alternative splicing events in the modulation of trophoblast cell biology. Here, we evaluated the expression of the alternative splicing regulator Rbfox2 in the pre‐ and post‐placentation period in mouse pregnancies in both healthy and pathological settings. Method of study: Immunofluorescence analysis of Rbfox2 expression in mouse implantation sites collected during the pre‐placentation period (E5‐E7) and post‐placentation (E13). Results: We identified a progressive increase of Rbfox2 levels throughout the peri‐implantation period with a shift from a cytoplasmatic expression on E5‐E6 to a predominantly nuclear expression on E7, together with a prominent expression of this factor in both subcellular compartments of the primitive placenta. Our results further showed that in contrast to healthy gestations, Rbfox2 expression decreased in preeclamptic models during the post‐placentation period. Finally, we further demonstrated enhanced expression of Rbfox2 proteins in allogeneic pregnancy compared to syngeneic models. Conclusions: Our findings uncover a novel role for Rbfox2‐controlled splicing events in the modulation of trophoblast function, with potential implications for the pathogenesis of preeclampsia and other pregnancy complications originated from defective placentation. [ABSTRACT FROM AUTHOR]

Problem: From conception, a delicate regulation of galectins, a family of carbohydrate‐binding proteins, is established to ensure maternal immune tolerance in pregnancy. Though galectin‐3 (gal‐3), the only chimera‐type galectin, is abundantly expressed at the feto‐maternal interface; the physiological role of this lectin during pregnancy remains to be fully elucidated and requires further investigation. Method of study: In this study, we analyzed serum gal‐3 levels during the course of healthy gestation. Trophoblast functions were evaluated upon gal‐3 exogenous stimulation using trophoblastic cell lines (e.g. , HIPEC65, SGHPL‐4, and BeWo cells). Finally, we investigated variations in peripheral gal‐3 levels associated with the development of spontaneous abortion and gestational diabetes mellitus (GDM). Results: Gal‐3 circulating levels increased as normal pregnancy progressed. In vitro experiments showed that exogenous gal‐3 positively regulated trophoblast functions inducing invasion, tube formation, and fusion. Compared with normal pregnant women, circulating gal‐3 levels were significantly decreased in patients who developed GDM. Conclusion: Our results reveal a physiological role for gal‐3 during pregnancy, promoting proper trophoblast functions associated with healthy gestation. GDM is associated with a failure to increase circulating gal‐3 levels late in gestation. Thus, dysregulation of gal‐3 may indicate a contribution of the chimera‐type lectin to this adverse pregnancy outcome. [ABSTRACT FROM AUTHOR]

Problem Galectins influence the progress of pregnancy by regulating key processes associated with embryo-maternal cross talk, including angiogenesis and placentation. Galectin family members exert multiple roles in the context of hemochorial and epitheliochorial placentation; however, the galectin prolife in endotheliochorial placenta remains to be investigated. Method of study Here, we used immunohistochemistry to analyze galectin (gal)-1, gal-3 and gal-9 expression during early and late endotheliochorial placentation in two different species (dogs and cats). Results We found that during early feline gestation, all three galectin members were more strongly expressed on trophoblast and maternal vessels compared to the decidua. This was accompanied by an overall decrease of gal-1, gal-3 and gal-9 expressions in late feline gestation. In canine early pregnancy, we observed that gal-1 and gal-9 were expressed strongly in cytotrophoblast ( CTB) cells compared to gal-3, and no galectin expression was observed in syncytiotrophoblast ( STB) cells. Progression of canine gestation was accompanied by increased gal-1 and gal-3 expressions on STB cells, whereas gal-9 expression remained similar in CTB and STB. Conclusion These data suggest that both the maternal and fetal compartments are characterized by a spatiotemporal regulation of galectin expression during endotheliochorial placentation. This strongly suggests the involvement of the galectin family in important developmental processes during gestation including immunemodulation, trophoblast invasion and angiogenesis. A conserved functional role for galectins during mammalian placental development emerges from these studies. [ABSTRACT FROM AUTHOR]

Problem Multiparity status has been found to bring beneficial effects both to the maintenance of pregnancy and to the offspring; however, these effects have not been fully explained. We have previously reported that placentae obtained from multiparous females belonging to a syngeneic mouse crossbreeding showed an important increase in the number of placental macrophages, suggesting that they might constitute a protective subpopulation. Taking into account that macrophage-colony stimulating factor (M-CSF) and granulocyte-colony stimulating factor (G-CSF) have proved to modulate macrophage activity and that both factors and/or their receptors have been found at feto–maternal interface, in this paper we analyzed the presence of M-CSF and G-CSF in placental tissue employing the same multiparity mouse model in order to investigate the influence of parity status on local immunoregulation factors of macrophage activity. Method of study Three groups of mice (CBA/J × CBA/J) were analyzed: Primiparous Young, 3.0 ± 0.5 months old (PY); Primiparous Old, 8.5 ± 0.5 months old (PO) and Multiparous Old, 8.5 ± 0.5 months old, with three to four previous pregnancies (MO). The presence of M-CSF and G-CSF in placental tissue was analyzed by immunohistochemistry. Cytokeratin (CK) and vimentin (VIM) expression and PAS staining were also studied. Results The three groups showed a similar immunostaining pattern for M-CSF in the whole placental trophoblast, while the expression of G-CSF was significantly higher only in the spongy zone in the MO group. Furthermore, all the MO placentae showed 5–11 layers of cells adjacent to the decidua, where G-CSF and M-CSF were highly detected. Conversely, they constituted a thin layer in PY and PO placentae. These cells were proved to be CK(+) and VIM(−) thus demonstrating their trophoblast origin. In addition, the layers closer to the decidua were also PAS+ suggesting that they could be interstitial cells, a type of invading trophoblast. Conclusions In our mouse model, we observed an increase in the expression of G-CSF in placental spongiotrophoblast cells in multiparous females, which have been previously proposed as progenitors of the interstitial cells. Furthermore, this is the first report that indicates that parity status increases trophoblast invasion inducing a proliferative effect of the invading cells on the maternal tissue. We suggest that M-CSF and G-CSF secreted by these invading cells could favor the recruitment of macrophages to the trophoblast and might modulate their activity inducing a switch to a protective, non-inflammatory population. [ABSTRACT FROM AUTHOR]