Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy

Chatterjee, Piyali; Chiasson, Valorie L; Bounds, Kelsey R; Mitchell, Brett M.

doi:10.3389/fimmu.2014.00253

Cited by 250 publications

(213 citation statements)

References 82 publications

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“…Downregulation of IL-10 expression by T cells during pregnancy is not surprising, because currently it is widely accepted that inflammation is necessary for critical steps in early pregnancy (11). Regardless, the lower expression of IL-10 was not observed when we compared pregnant and nonpregnant individuals from PNG.…”

Section: Discussionmentioning

confidence: 63%

“…Conversely, controlled proinflammatory responses during pregnancy play a critical role in embryo implantation, placentation, parturition, and defense against infections. However, excessive maternal inflammatory responses are associated with adverse pregnancy outcomes (11). Thus, immunoregulation during pregnancy seems essential not only to tolerate fetal Ags, but also to resolve the necessary inflammatory processes (12).…”

mentioning

confidence: 99%

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Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

Requena

Barrios

Robinson

et al. 2015

The Journal of Immunology

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Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes. CD4+FOXP3+CD127low T cells (Tregs) were decreased in pregnant women in both countries but were not associated with malaria infection or poor delivery outcomes. An expansion of IFN-γ–producing cells and intracytoplasmic IFN-γ levels was found in pregnant compared with nonpregnant women only in Papua New Guinea. Increased CD4+IL-10+IFN-γ+ frequencies and Treg–IFN-γ production were found in women with current Plasmodium falciparum infection. Higher CD4+IL-10−IFN-γ+ T cells frequencies and production of proinflammatory cytokines (including TNF and IL-2) at recruitment (first antenatal visit) had a protective association with birth weight and future (delivery) P. falciparum infection, respectively. Higher intracellular IL-10 levels in T cells had a protective association with future P. falciparum infection and hemoglobin levels at delivery. The protective associations were found also with nonmalaria-specific T cell responses. Treg frequencies positively correlated with plasma eotaxin concentrations, but this subset did not express eotaxin receptor CCR3. Thus, an activated immune system during pregnancy might contribute to protection against malaria during pregnancy and poor delivery outcomes.

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Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

Requena

Barrios

Robinson

et al. 2015

The Journal of Immunology

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“…Proper regulation of expression of IL-10 in trophoblasts and uterine immune cells has been implicated in placental health and fetal development (59). We propose that our newly discovered PIF/TLR4/KSRP/let-7 signal transduction pathway and its mediated regulation of IL-10 expression may underlie PIF's mode of action on immune control and embryo development in the maternal-fetal interface.…”

Section: Discussionmentioning

confidence: 99%

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

Mueller

Zhou

Yang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

106

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Dysfunction and loss of neurons are the major characteristics of CNS disorders that include stroke, multiple sclerosis, and Alzheimer's disease. Activation of the Toll-like receptor 7 by extra-cellular micro-RNA let-7, a highly expressed microRNA in the CNS, induces neuronal cell death. Let-7 released from injured neurons and immune cells acts on neighboring cells, exacerbating CNS damage.Here we show that a synthetic peptide analogous to the mammalian PreImplantation factor (PIF) secreted by developing embryos and which is present in the maternal circulation during pregnancy inhibits the biogenesis of let-7 in both neuronal and immune cells of the mouse. The synthetic peptide, sPIF, destabilizes KH-type splicing regulatory protein (KSRP), a key microRNA-processing protein, in a Toll-like receptor 4 (TLR4)-dependent manner, leading to decreased production of let-7. Furthermore, s.c. administration of sPIF into neonatal rats following hypoxic-ischemic brain injury robustly rescued cortical volume and number of neurons and decreased the detrimental glial response, as is consistent with diminished levels of KSRP and let-7 in sPIF-treated brains. Our results reveal a previously unexpected mechanism of action of PIF and underscore the potential clinical utility of sPIF in treating hypoxic-ischemic brain damage. The newly identified PIF/TLR4/KSRP/ let-7 regulatory axis also may operate during embryo implantation and development.

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“…[35][36][37] Systemic inflammation during pregnancy may lead to premature rupture of membranes, preterm labor, and ultimately PTD. 35,[37][38][39][40][41][42][43][44] Therefore, systemic inflammation may be the pathway by which perceived neighborhood safety and depressive symptoms impact PTD. Future research needs to examine the impact of systemic inflammation on the relationships among perceived neighborhood safety, depressive symptoms, and PTD.…”

Section: Discussionmentioning

confidence: 99%

Neighborhood Context and Preterm Delivery among African American Women: the Mediating Role of Psychosocial Factors

et al. 2016

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Preterm delivery (PTD), or birth before 37 completed weeks of gestation, is a serious public health issue, and racial disparities persist. In a recently published study, perceptions of the residential environment (or neighborhood context) were associated with PTD rates among urban African American women with low educational attainment (≤12 years); however, the mechanisms of these associations are unknown. Given this gap in the literature, we used data from the Life Influences on Fetal Environments Study of postpartum African American women from Metropolitan Detroit, Michigan (2009Michigan ( -2011 n = 399), to examine whether psychosocial factors (depressive symptomology, psychological distress, and perceived stress) mediate associations between perceptions of the neighborhood context and PTD. Validated scales were used to measure women's perceptions of their neighborhood safety, walkability, healthy food availability (higher=better), and social disorder (higher=more disorder). The psychosocial indicators were measured with the Center for Epidemiologic Studies-Depression Scale, Kessler's Psychological Distress Scale (K6), and Cohen's Perceived Stress Scale. Statistical mediation was assessed using an unadjusted logistic regression-based path analysis for estimating direct and indirect effects. The associations between perceived walkability, food availability, and social disorder were not mediated by psychosocial factors. However, perceptions of neighborhood safety were inversely associated with depressive symptoms which were positively associated with PTD rates. Also, higher perceived neighborhood social disorder was associated with higher PTD rates, net of the indirect paths through psychosocial factors. Future research should identify other mechanisms of the perceived neighborhood context-PTD associations, which would inform PTD prevention efforts among high-risk groups.

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Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy

Cited by 250 publications

References 82 publications

Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

Neighborhood Context and Preterm Delivery among African American Women: the Mediating Role of Psychosocial Factors

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