Regulated suppression of NF-κB throughout pregnancy maintains a favourable cytokine environment necessary for pregnancy success

Hadfield, Katrina A.; McCracken, Sharon A.; Ashton, Anthony W.; Nguyen, Tuan Nghia; Morris, Jonathan M.

doi:10.1016/j.jri.2010.11.008

Cited by 34 publications

(37 citation statements)

References 41 publications

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“…NF-κB plays a crucial role in Th1 differentiation, clonal expansion and the production of IFN γ [11] as well as in graft rejection in the mouse [12]. The p65:p50 heterodimer is the most common active form of NF-κB and we have shown that expression of p65 is reduced in T-cells throughout pregnancy [13]. This suppression inhibits T-bet expression and ultimately attenuates Th1 cytokine production in response to PMA stimulation [13].…”

Section: Introductionmentioning

confidence: 85%

“…The p65:p50 heterodimer is the most common active form of NF-κB and we have shown that expression of p65 is reduced in T-cells throughout pregnancy [13]. This suppression inhibits T-bet expression and ultimately attenuates Th1 cytokine production in response to PMA stimulation [13]. In addition, since Th17 cells require activation of NF-κB for appropriate differentiation, suppression of p65 in pregnancy likely limits the number of functional Th17 cells.…”

Section: Introductionmentioning

confidence: 95%

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NF-kB Regulation in T-cells in Pregnancy is Mediated via Fas/FasL Interactions: The Signal for which is Derived from Exosomes Present in Maternal Plasma

McCracken¹,

Hadfield²,

Yenson³

et al. 2016

Reproductive Immunol Open Acc

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Background: Regulated suppression of maternal Th1 immunity is necessary for normal pregnancy since inappropriate Th1 responses results in increased pregnancy loss and complications including intrauterine growth restriction (IUGR). We have shown that suppression of the p65 subunit of NF-κB in maternal T-cells underlies this change in T-cell responses. This study aimed to determine mechanism(s) that control p65 suppression.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 95%

NF-kB Regulation in T-cells in Pregnancy is Mediated via Fas/FasL Interactions: The Signal for which is Derived from Exosomes Present in Maternal Plasma

McCracken¹,

Hadfield²,

Yenson³

et al. 2016

Reproductive Immunol Open Acc

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“…TLR-mediated cell signaling cascades involve the cytokine inductor nuclear factor kappa b (NFKB) and interferon regulatory factors (IRFs) to induce type I interferons (IFNs) (Kumar et al 2009). Both of these pathways are actively regulated in the female reproductive tract, and their deregulation leads to infertility and disease (Spencer et al 1998, King et al 2001, Fleming et al 2009, Ross et al 2010, Hadfield et al 2011, Maybin et al 2011.…”

Section: Introductionmentioning

confidence: 99%

“…Gestation has been considered a Th2 or antiinflammatory environment, achieved through suppression of the NFKB pathway and increased abundance of interleukin 10 (IL10), IL4, or IL5 (Piccinni et al 2001, Hadfield et al 2011. However, Th1 (pro-inflammatory) molecules such as tumor necrosis factor alpha (TNFA) and IFNgamma (IFNG) are also necessary for uterine receptivity, implantation, and placental development in some species (Ashkar & Croy 2001, Hess et al 2007, Paulesu et al 2010, Warning et al 2011, Granot et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Ruiz-Gonzalez¹,

Minten²,

Wang³

et al. 2015

Reproduction

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Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction.In Study 1, we demonstrated that abundance of ovine TLR1-TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1-TLR3, TLR5-TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1-TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.

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“…In the peripheral circulation the mechanisms that regulate this adaptation are not fully understood. Dr McCracken and colleagues have shown that NFkappaB in central to the regulation of Th1 immunity [4] and have shown that suppression of NF-κB controls the production of Th1 cytokines thus biasing Th2 cytokine production.…”

mentioning

confidence: 99%

Are Exosomes A Viable Therapy For Pregnancy Complications?

McCracken¹

2017

Reproductive Immunol Open Acc

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Regulated suppression of NF-κB throughout pregnancy maintains a favourable cytokine environment necessary for pregnancy success

Cited by 34 publications

References 41 publications

NF-kB Regulation in T-cells in Pregnancy is Mediated via Fas/FasL Interactions: The Signal for which is Derived from Exosomes Present in Maternal Plasma

NF-kB Regulation in T-cells in Pregnancy is Mediated via Fas/FasL Interactions: The Signal for which is Derived from Exosomes Present in Maternal Plasma

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Are Exosomes A Viable Therapy For Pregnancy Complications?

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