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- Abelius, Martina S, et al.
(författare)
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The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity
- 2015
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Ingår i: American Journal of Reproductive Immunology. - : Wiley-Blackwell. - 1046-7408 .- 1600-0897. ; 73:5, s. 445-459
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.
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| 2. |
- Barranco, Isabel, et al.
(författare)
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The Seminal Plasma of the Boar is Rich in Cytokines, with Significant Individual and Intra-Ejaculate Variation
- 2015
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Ingår i: American Journal of Reproductive Immunology. - : WILEY-BLACKWELL. - 1046-7408 .- 1600-0897. ; 74:6, s. 523-532
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Tidskriftsartikel (refereegranskat)abstract
- Problem The boar, as human, sequentially ejaculates sperm-rich and sperm-poor fractions. Seminal plasma (SP) spermadhesins (PSP-I/PSP-II) induce a primary endometrial inflammatory response in female sows, similar to that elicited by semen deposition in other species, including human. However, the SP is also known to mitigate such response, making it transient to allow for embryo entry to a cleansed endometrium. Although cytokine involvement has been claimed, the exploration of cytokines in different SP fractions is scarce. This study determines Th1, Th2, Th17 and Th3 cytokine profiles in specific ejaculate SP fractions from boars of proven fertility. Methods SP samples from the sperm-rich fraction (SRF) and the sperm-poor post-SRF fraction (post-SRF) of manually collected ejaculates from eight boars (four ejaculates per boar) were analysed by commercial multiplex bead assay kits (Milliplex MAP, Millipore, USA) for interferon-gamma, interferon gamma-induced protein 10, macrophage-derived chemokine, growth-regulated oncogene, granulocyte-macrophage colony-stimulating factor, monocyte chemo-attractant protein-1, interleukins (IL)-6, IL-8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-beta 1-beta 3. Results Cytokine concentrations differed between the ejaculate fractions among boars, being highest in the post-SRF. Conclusion Boar SP is rich in Th1, Th2, Th17 and Th3 cytokines, with lowest concentrations in the sperm-peak-containing fraction, indicating its main immune influence might reside in the larger, protein-rich sperm-poor post-SRF.
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| 4. |
- Boij, Roland, et al.
(författare)
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Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
- 2015
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Ingår i: American Journal of Reproductive Immunology. - : WILEY-BLACKWELL. - 1046-7408 .- 1600-0897. ; 74:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.
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| 5. |
- Bourlev, Vladimir, 1947-, et al.
(författare)
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Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain
- 2018
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 80:3
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Tidskriftsartikel (refereegranskat)abstract
- ProblemChronic pelvic pain (CPP) causes compromised the quality of life in women with endometriosis and is often attributed to local inflammation and ingrowth of nerve fibers. In this pilot study, we aimed to investigate whether the inflammation‐related vasoactive intestinal peptide (VIP) and interleukin (IL)‐6 were increased in affected patients.Method of studyEndometrial and endometriotic tissue biopsy specimens, and serum and peritoneal fluid (PF) samples, were obtained from 85 endometriosis patients and 53 controls. VIP and IL‐6 analysis and measurement of microvessel density in tissue were performed using immunohistochemistry, Western blotting, RT‐qPCR, and ELISA.ResultsCompared with controls, VIP transcript and protein levels were increased in endometrium from endometriosis patients and further elevated in patients with CPP. In addition, microvessel density, a measurement of angiogenic activity, was increased in the endometrium and in endometriosis lesions in the same subset of patients. Serum and PF levels of VIP and IL‐6 were higher in women with endometriosis and CPP compared with endometriosis patients who reported no chronic pain.ConclusionVasoactive intestinal peptide is upregulated in endometriosis patients reporting chronic pain. Increased microvessel density in tissue and peritoneal fluid concentrations of IL‐6 indicate an elevated inflammation in the pelvic microenvironment of these patients.
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| 6. |
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| 7. |
- Erlandsson, Lena, et al.
(författare)
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Inventory of Novel Animal Models Addressing Etiology of Preeclampsia in the Development of New Therapeutic/Intervention Opportunities.
- 2016
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1600-0897 .- 1046-7408. ; 75:3, s. 402-410
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Forskningsöversikt (refereegranskat)abstract
- Preeclampsia is a pregnancy-related disease afflicting 3-7% of pregnancies worldwide and leads to maternal and infant morbidity and mortality. The disease is of placental origin and is commonly described as a disease of two stages. A variety of preeclampsia animal models have been proposed, but all of them have limitations in fully recapitulating the human disease. Based on the research question at hand, different or multiple models might be suitable. Multiple animal models in combination with in vitro or ex vivo studies on human placenta together offer a synergistic platform to further our understanding of the etiology of preeclampsia and potential therapeutic interventions. The described animal models of preeclampsia divide into four categories (i) spontaneous, (ii) surgically induced, (iii) pharmacologically/substance induced, and (iv) transgenic. This review aims at providing an inventory of novel models addressing etiology of the disease and or therapeutic/intervention opportunities.
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| 12. |
- Musilova, Ivana, et al.
(författare)
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Amniotic fluid pentraxins: Potential early markers for identifying intra-amniotic inflammatory complications in preterm pre-labor rupture of membranes.
- 2018
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Ingår i: American journal of reproductive immunology (New York, N.Y. : 1989). - : Wiley. - 1600-0897 .- 1046-7408. ; 79:5
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Tidskriftsartikel (refereegranskat)abstract
- In this study, pentraxin 3 (PTX3), C-reactive protein (CRP), and serum amyloid P component (SAP) concentrations in the amniotic fluid of women with preterm pre-labor rupture of membranes (PPROM) were evaluated based on evidence of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI. A total of 149 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid PTX3, SAP, and CRP concentrations were assessed using enzyme-linked immunosorbent assay. PTX3 and CRP concentrations were higher in women with MIAC, IAI, and microbial-associated IAI than in women without these conditions. SAP concentrations were only higher in the presence of IAI and microbial-associated IAI. Amniotic fluid PTX3 concentrations of 11ng/mL were found to be the best value for identifying the presence of microbial-associated IAI and IAI in women with PPROM. To conclude, amniotic fluid pentraxins are involved in intra-amniotic inflammatory responses in pregnancies complicated by PPROM.
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| 13. |
- Sharma, Surendra, et al.
(författare)
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Obituary: Leif Matthiesen, MD, PhD (1954‐2017)
- 2017
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Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 78:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Leif Matthiesen, an evergreen member and supporter of the American Society for Reproductive Immunology (ASRI), died on April 29, 2017, following a hard fought battle with glioblastoma. We all hoped that Leif being a fearless person and a fun‐loving physician scientist would beat all the odds against this dreaded disease and come out of it with flying colors. Alas, our hopes were given a serious thought by the Almighty. We as a community of friends and scientific colleagues are saddened by the loss of such a wonderful human being and a noteworthy member of the ASRI.
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| 14. |
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| 15. |
- Solders, M., et al.
(författare)
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Mature naive B cells are retained in the placental intervillous blood and positively associate with specific chemokines in full-term healthy pregnancy
- 2019
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 82:3
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Tidskriftsartikel (refereegranskat)abstract
- Problem Circulating B-cell numbers are lower during pregnancy compared with non-pregnant women, but the underlying reasons for this are unknown. Pregnancy-related hormones could influence B-cell lymphopoiesis in the bone marrow, but B cells may also be recruited to the placenta. To investigate the latter, we examined whether the proportions of total B cells and B cells at different maturational stages in placental intervillous blood (IVB) differ compared with peripheral blood (PB). Method of study From 23 paired samples of PB and IVB following full-term healthy pregnancies, total B cells and immature/transitional, mature/naive, and memory B cells were identified by flow cytometry. Chemokine levels in blood were analyzed using a Luminex assay. Placental explant-derived supernatant was assayed for B-cell chemotactic activity. Results The proportions of total B cells and mature/naive B cells were significantly higher in IVB relative to PB, while the fractions of immature/transitional cells and memory B cells were higher in PB. Multivariate factor analysis demonstrated that a specific chemokine profile in IVB, including CCL20, positively associated with higher proportions of mature/naive B cells in the intervillous space. All B cells expressed CCR6, the corresponding receptor for CCL20, but the intensity of CCR6 expression was significantly higher in mature/naive B cells relative to immature/transitional B cells. Migration assays showed that placental explant-derived supernatants attract B cells. Conclusion These results indicate that B cells, and mature/naive B cells in particular, are retained in the intervillous blood in response to certain chemokines produced by the placenta during late healthy pregnancy.
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| 16. |
- Svensson-Arvelund, Judit, 1982-, et al.
(författare)
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The Role of Macrophages in Promoting and Maintaining Homeostasis at the Fetal-Maternal Interface
- 2015
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Ingår i: American Journal of Reproductive Immunology. - : Wiley: 12 months. - 1046-7408 .- 1600-0897. ; 74:2, s. 100-109
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Forskningsöversikt (refereegranskat)abstract
- A successful pregnancy requires that the maternal immune system adapts properly to avoid rejection of the semi-allogeneic fetus without compromising the ability to protect the mother and the fetus against infections. In this review, we describe the role of decidual macrophages in creating a homeostatic environment at the fetal-maternal interface. We also discuss their role in pregnancy complications as well as future possibilities to modulate macrophage function therapeutically. Decidual macrophages are enriched at the fetal-maternal interface and play a major role in the regulation of inflammatory responses and the maintenance of a tolerant environment. Their function is, however, not restricted to immune tolerance, but extends to include functions such as the recognition and clearance of infections, the clearance of apoptotic debris, and tissue remodeling. Decidual macrophages seem to largely function as tissue-resident macrophages that are crucial for maintaining homeostasis and reproductive success.
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| 17. |
- Vinnars, Marie-Therese, et al.
(författare)
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Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
- 2018
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- ProblemPre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta. Method of studyThe cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR. ResultsThe cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta. ConclusionThe destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
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