Wound healing: time to look for intelligent, ‘natural’ immunological approaches?

Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1β. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1β in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth.     

Immune activation by nucleic acids: A role in pregnancy complications

Cell‐free self‐DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell‐free foetal DNA is associated with pregnancy complications and a higher risk for foetal rejection. Cell‐free foetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps (NETs) and in extracellular vesicles (EVs). In several pregnancy complications, cell‐free foetal DNA triggers the production of proinflammatory cytokines, and this production results in a cellular and humoral immune response. This review discusses preeclampsia, systemic lupus erythematosus, foetal growth restriction, gestational diabetes, rheumatoid arthritis and obesity in pregnancy from an immunological point of view and closely examines the different pathways that result in maternal inflammation. Understanding the role of cell‐free nucleic acids, as well as the biogenesis of NETs and EVs, will help us to specify their functions or targets, which seem to be important in pregnancy complications. It is still not clear whether higher concentrations of cell‐free nucleic acids in the maternal circulation are the cause or consequence of various complications. Therefore, further clinical studies and, even more importantly, animal experiments that focus on the involved immunological pathways are needed.     

Pregnancy IFN-gamma responses to foetal alloantigens are altered by maternal allergy and gravidity status

Background: During pregnancy, variations in maternal–foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies. Methods: For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36‐week gestation and 6‐week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin‐6 (IL‐6), IL‐10, IL‐13 and (interferon‐γ) IFN‐γ] at each time point towards foetal mononuclear cells. Results: Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6‐week pp. The ratio of maternal IFN‐γ/IL‐13 and IFN‐γ/IL‐10 responses were lower during pregnancy. Allergic mothers had lower IFN‐γ responses at each time‐point during pregnancy with the greatest difference in responses observed at 36‐week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN‐γ responses of allergic multigravid mothers were significantly lower than nonallergic multigravid mothers during pregnancy. Conclusions: During normal pregnancy, peripheral T‐cell cytokine responses to foetal alloantigens may be altered by both allergic status of the mother and previous pregnancies. These factors could influence the cytokine milieu experienced by the foetus and will be further explored in the development of allergic disease during early life.     

产前应激对子代的影响及潜在作用机制

Inappropriate diet and stress in maternal pregnancy may affect the development of the offspring. Brain dysfunction and some chronic diseases such as obesity and diabetes in offspring are associated with the factors during maternal pregnancy. Many researches focused on how prenatal stress affected cognitive function and behavior of the offspring and how nutritional modulation might prevent the pathogenesis of such diseases. Here we summarize the effects of prenatal stress on the offspring and the potential mechanism, like hypothalamus-pituitary-adrenal axis(HPA), oxidative stress, apoptosis and inflammation, and the prevention of nutrient to offspring dysfunction by prenatal stress, based on our previous work and some existing references.     

Childhood allergy susceptibility: The role of the immune system development in the in-utero period

Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism’s structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events – which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function – can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review.(199 words)     

Lipopolysaccharide‐binding protein and leptin are associated with stress‐induced interleukin‐6 cytokine expression ex vivo in obesity

Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity‐associated inflammation. This study examined whether obese subjects would elicit a greater host immune response (IL‐6 mRNA and cytokine) to lipopolysaccharide (LPS) in response to mental stress. Blood samples for LPS‐stimulated IL‐6 mRNA and cytokine were collected prior to and following mental stress. Results showed that obese subjects elicited a greater LPS‐induced IL‐6 along with its mRNA expression following mental stress compared to normal‐weight subjects. Stress‐induced IL‐6 cytokine response to LPS was correlated with the baseline levels of plasma LPS binding protein (LBP) and leptin. These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress.     

Alterations in behavior in adult offspring mice following maternal inflammation during pregnancy

Maternal intrauterine inflammation during pregnancy poses a major threat of neurodevelopmental brain damage in offspring and may cause poor cognitive and perceptual outcomes. In mice, we have previously shown that maternal inflammation induced by lipopolysaccharide (LPS) at gestation day 17th increased the levels of the pro-inflammatory cytokine IL-6 in the fetal brain. In this study, we used the same system and examined the effect of short, systemic maternal inflammation on anxiety and social behavior of the offspring. Adult offspring from the maternal inflammation group showed increased anxiety, as indicated by the elevated plus maze. Social interaction among offspring from the test groups was examined when two unfamiliar mice from different litters were introduced into a new home-cage. Offspring from the maternal inflammation group showed reduced activity, indicating increased fear. In addition, offspring from the maternal inflammation group were less aggressive towards their cagemates and they spent a significantly longer time trimming the whiskers of their cagemates during the first 30 min of their interaction, compared to offspring from the control group. Our data suggest that short systemic maternal inflammation have long-lasting consequences on the adult mouse stress and social behavior.     

Maternal obesity and the developmental programming of hypertension: a role for leptin

Mother–child cohort studies have established that both pre‐pregnancy body mass index (BMI) and gestational weight gain are independently associated with cardio‐metabolic risk factors in young adult offspring, including systolic and diastolic blood pressure. Animal models in sheep and non‐human primates provide further evidence for the influence of maternal obesity on offspring cardiovascular function, whilst recent studies in rodents suggest that perinatal exposure to the metabolic milieu of maternal obesity may permanently change the central regulatory pathways involved in blood pressure regulation. Leptin plays an important role in the central control of appetite, is also involved in activation of efferent sympathetic pathways to both thermogenic and non‐thermogenic tissues, such as the kidney, and is therefore implicated in obesity‐related hypertension. Leptin is also thought to have a neurotrophic role in the development of the hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity are associated with permanently altered hypothalamic structure and function. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper‐responsiveness and hypertension acquired in the early stages of development. Experimental neonatal hyperleptinaemia in naive rat pups provides further evidence of heightened sympathetic tone and proof of principle that hyperleptinaemia during a critical window of hypothalamic development may directly lead to adulthood hypertension. Insight from these animal models raises the possibility that early‐life exposure to leptin in humans may lead to early onset essential hypertension. Ongoing mother–child cohort and intervention studies in obese pregnant women provide a unique opportunity to address associations between maternal obesity and offspring cardiovascular function. The goal of the review is to highlight the potential importance of leptin in the developmental programming of hypertension in obese pregnancy.     

Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers

The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4⁺ Foxp3⁺ regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity.     

Maternal obesity, metabolic disease, and allostatic load

Maternal obesity is a risk factor for many metabolic diseases for the mother, both during gestation and post partum, and for the child in later life. Obesity and pregnancy both result in altered physiological states, significantly different from the state of the non-obese, non-reproductive adult female. The concept of allostasis may be more appropriate for understanding the physiology of both pregnancy and obesity. In pregnancy these altered physiological states are adaptive, in both the evolutionary and physiological senses of the word. Obesity, however, represents a state outside of the adaptive evolutionary experience of our species. In both cases the altered physiological state derives at least in part from signals from an active endocrine organ. In obesity this is adipose tissue, and in pregnancy it is the placenta. The signaling molecules from adipose tissue and placenta all have multiple functions and can affect multiple organ systems. Placenta acts as a central regulator of metabolism for both the maternal and fetal compartments, in essence acting as a "third brain" during pregnancy. Both adipose tissue and placenta express many proinflammatory cytokines; obesity and pregnancy are states of low-grade inflammation. Both obesity and pregnancy are also states of insulin resistance, and maternal obesity is associated with fetal insulin resistance. We argue that obesity during pregnancy leads to sustained and inappropriate activation of normally adaptive regulatory circuits due in part to competing and conflicting signaling from adipose tissue and placenta. This results in allostatic load, leading to the eventual break down of regulatory mechanisms. The result is impaired metabolic function of the mother, and altered development of metabolic systems and potentially altered neural appetite circuits for the offspring.     

Macrophages—common culprit in obesity and asthma

Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve distinct innate immunological metabolic functions. IFN‐γ or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or “classically activated” phenotype that participates in defense against intracellular pathogens. IL‐4, IL‐13, or chitin polarizes macrophages toward the M2, or “alternatively activated” phenotype, which defends against multicellular nematodes and fungi. As macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here, we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1‐mediated inflammation in adipose tissue enhances M2‐mediated inflammation in the asthmatic lung.     

Preeclampsia and health risks later in life: an immunological link

Pregnancy represents a period of physiological stress, and although this stress is experienced for a very modest portion of life, it is now recognized as a window to women’s future health, often by unmasking predispositions to conditions that only become symptomatic later in life. In normal pregnancy, the mother experiences mild metabolic syndrome-like condition through week 20 of gestation. A pronounced phenotype of metabolic syndrome may program pregnancy complications such as preeclampsia. Preeclampsia is a serious complication with a myriad of manifestations for mother and offspring. This pregnancy syndrome is a polygenic disease and has been now linked to higher incidence of cardiovascular disease, diabetes, and several other disorders associated with vulnerable organs. Furthermore, the offspring born to preeclamptic mothers also exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases in later life. The etiology of preeclampsia is thought to be primarily associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross-talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Since normal pregnancy is associated with a sequence of events represented by temporal events of inflammation (implantation), anti-inflammation (gestation), and inflammation (parturition), it is quite possible that unscheduled alterations in these regulatory responses may lead to pathologic consequences. Although it is not clear whether immunological alterations occur early in pregnancy, it is proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. This review will focus on important aspects of the immune system that coordinate with placental dysfunction to program preeclampsia and influence health in later life.     

Is There a Maternally Induced Immunological Imprinting Phase à la Konrad Lorenz?

In mammals, IgG antibodies are transferred from mothers to the offspring. Since these maternal antibodies result mainly from thymus-dependent immune responses which have undergone immune maturation through somatic hypermutations, they represent the highest quality of the collective maternal immunological experience. Maternal antibodies not only confer passive immunity as long as the newborn's immune system has not fully developed, but also exert an active stimulation as indicated by their regulatory influence on isotype expression, long-term idiotypic alterations, determination of the adult B and T cell repertoire, induction of antigen reactive IgM as well as an affinity enhancement of a proportion of early primary antibodies. The fact that several of these features can only be induced during limited sensitive periods shortly after birth is reminiscent of the behavioural imprinting as defined by Konrad Lorenz. We therefore propose that during early ontogeny there is an immunological imprinting phase with characteristics analogous to behavioural imprinting: (i) the internal imprinting effect is induced by external signals, (ii) in contrast to normal learning, immunological imprinting is also only possible during certain development phases and (iii) it is characterised by an (almost) irreversible result. Hence, if particular immunological experiences are only possible during such sensitive phases, maternal immunoglobulins and consequently the mother's immunological experience is of prime importance for the start of the ontogenetic development of the immune system.     

Inherent maternal type 2 immunity: Consequences for maternal and offspring health

An inherent elevation in type 2 immunity is a feature of maternal and offspring immune systems. This has diverse implications for maternal and offspring biology including influencing success of pregnancy, offspring immune development and maternal and offspring ability to control infection and diseases such as allergies. In this review we provide a broad insight into how this immunological feature of pregnancy and early life impacts both maternal and offspring biology. We also suggest how understanding of this axis of immune influence is and may be utilised to improve maternal and offspring health.     

Suppression of Allergen‐Specific IgE in Offspring After Preconceptional Immunisation: Maternal,Paternal and Genetic Influences

Immunisation of female mice with the allergen ovalbumin (OVA) during pregnancy reduces the OVA‐specific IgE response in adult offspring. To approach primary prevention strategies for allergy, we investigated to what extent genetic, paternal and maternal factors influence this suppressive effect on allergic sensitisation in offspring and investigated the possibility of pregestational immunisation. Maternal allergen immunisation reduced OVA‐specific IgE levels in immunised offspring, even after maternal immunisation up to 8 weeks before conception without further allergen exposure. Immunisation of immunodeficient BALB/c severe combined immune deficiency (SCID) dams mated with wild type males did not lead to IgE suppression in offspring, indicating the importance of a functional maternal immune system. Immunisation of male mice before the relevant spermatogenesis did not cause antibody suppression in offspring. OVA‐specific IgG1, presumably of maternal origin, was present in naïve offspring only from immunised dams and was associated with suppressed IgE responses after offspring immunisation. The IgE‐suppressive effect of maternal immunisation was demonstrated in all three immunocompetent strains tested (NIH/OlaHsd, BALB/cA and C57BL/6 mice). In conclusion, suppression of allergen‐specific IgE production in offspring could not be induced by paternal immunisation, and genetic factors were of minor importance. In contrast, we demonstrate the necessity of maternal factors, possibly allergen‐specific IgG1, resulting from a functional adaptive immune response, for the IgE‐suppressive effect in offspring. These maternal factors could be induced by immunisation of female mice even before conception.     

Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma

Background Maternal, more than paternal, asthma is a risk factor for the development of asthma in children. Recently, epidemiologic studies have shown that environmental exposures during pregnancy might influence the development of childhood asthma and allergies. Objective The aim of the present study was to investigate whether the induction of tolerance against a specific antigen during pregnancy prevents in the offspring the development of allergic asthma in response to this antigen. Methods Balb/c mice were orally tolerized with ovalbumin (OVA) during pregnancy. The offspring of tolerized and naïve mothers were immunized with OVA at 6 weeks and 4 months of age and analysed in our murine asthma model. Results While the offspring of naïve mice developed increased AHR, eosinophilic airway inflammation, T‐helper type 2 cytokine production and high serum IgE levels in response to OVA sensitization, the offspring of tolerized mice were almost completely protected from asthma, even when immunized as late as 4 months after birth. Breastfeeding was crucial for protection because tolerance was only observed when the offspring were nursed by their own mothers and not when nursed by naïve wet‐nurses. Allergen‐specific IgG₁ antibodies were exclusively increased in the breast milk of tolerant mothers and serum of protected pups, indirectly supporting its important role in tolerance transfer from the mother to the offspring. Sensitization of the F1 generation from OVA‐tolerized mothers with a heterologous allergen enhanced the immune response to this antigen. Conclusion Our results demonstrate that mucosal allergen contact during pregnancy modifies the asthma and allergy risk of the offspring mediated via breast milk. This observation may suggest that the time window for primary prevention strategies starts even before early childhood during pregnancy.     

Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring

Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring.     

Genetic selection of embryos that later develop the metabolic syndrome

THE BARKER HYPOTHESIS: Is an excellent explanation of the process where human and animal foetuses exposed to malnutrition, either by maternal malnutrition or placental insufficiency, are metabolically programmed, with selective stunting of cell differentiation and organ growth. With the postnatal excess of nutrition observed in developed countries, this irreversible programming causes metabolic syndrome, including obesity, type 2 diabetes, and hypertension. Metabolic programming involves epigenetic changes including imprinting which might be transmitted through more than one generation rather than being completely re-set or erased during reproduction. The Barker hypothesis was supported by epidemiological data that recognised no excess fetal or postnatal mortality when pregnant women were starved during the Dutch famine in World War II. This argued against the "thrifty genotype" theory introduced in 1962, which proposed that starvation selected against members of the population with less "thrifty" genes, but the survivors who had "thrifty" genes developed metabolic syndrome if they were subsequently over-nourished. EMBRYONIC/FETAL SELECTION: Embryos or early foetuses could be selected very early in pregnancy on the basis of their genotype, by maternal malnutrition, hypertension, obesity or other causes of placental insufficiency. The genotype that allows embryos, or cells within them, to survive a less hospitable environment in the decidua after implantation might contribute to the later development of metabolic syndrome. This article hypothesises that an adverse intrauterine environment, caused by maternal malnutrition or placental insufficiency, kills a proportion of embryos and selects a surviving population of early embryos whose growth in utero is retarded by their genotype, their environment or a combination of both. The metabolic syndrome follows if the offspring is over-nourished later in life. The embryonic selection hypothesis presented here could be tested by using single nucleotide polymorphism (SNP) microarrays to study adults who had a history of intrauterine growth retardation (IUGR) and subsequent metabolic syndrome. Their SNP array could be compared with their parents and unaffected unrelated or related controls. If there were no selection based on a "thrifty genotype", all parental sequences would be expected to appear in their surviving children, whether or not they had IUGR or developed metabolic syndrome. SNP sequences present in parents or controls but missing from adult offspring with metabolic syndrome who had IUGR, could be associated with or linked to genes that influence susceptibility to metabolic syndrome. This hypothesis proposes that missing genotypes would be lost if the embryos that inherited them died very early in pregnancy.     

Maternal allergen immunisation to prevent sensitisation in offspring: Th2-polarising adjuvants are more efficient than a Th1-polarising adjuvant in mice

Background

Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period.

Results

Maternal immunization with OVA showed increased levels of FcγRIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-γ-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced FcγRIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers.

Conclusion

Maternal immunization upregulates the inhibitory FcγRIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.     

Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring

Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring.