| 1. |
- Gustafsson, Katarina, et al.
(författare)
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Isolation and partial characterization of an interleukin-1-like factor from rat testis interstitial fluid.
- 1988
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378 .- 1872-7603. ; 14:2, s. 139-150
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Tidskriftsartikel (refereegranskat)abstract
- Testicular interstitial fluid (ISF) was collected by in vivo perfusion of rat testes and analyzed for the presence of interleukin-1 (IL-1) activity by utilizing a murine thymocyte proliferation assay. IS obtained from nine rats were all positive with dose-response curves of IL-1 activity similar to those produced by rat testicular aqueous extracts, rat macrophage IL-1 and human recombinant IL-1α. Chromatofocusing of pooled ISF revealed a single peak of IL-1 activity with an estimated isoelectric point of 6.1–6.3. HPLC size exclusion chromatography demonstrated two active peaks with apparent molecular ratios Mr of 15,000–18,000 and 5000–7000, respectively. The molecular properties of the 15,000–18,000 Mr component are very similar to those of an IL-1-like factor previously isolated from seminiferous tubules. Our results indicate that the testicular IL-1-like factor is secreted by the seminiferous tubules into the interstitial tissue. Its function in the testicular interstitium is unknown but it might be relevant for the tendency to testicular relapse of childhood lymphocytic leukemia.
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| 2. |
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| 3. |
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| 4. |
- Matthiesen, Leif, 1954-, et al.
(författare)
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In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy
- 2002
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Ingår i: Journal of Reproductive Immunology. - 0165-0378 .- 1872-7603. ; 58:1, s. 49-59
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines, interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-a and interferon (IFN)-? during normal pregnancy. Material and methods: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. Results: The numbers of IFN-? and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-a and IL-10. Conclusion: Our studies demonstrated increased numbers of both IFN-? and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-? on systemic immunity during pregnancy.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Abelius, Martina, et al.
(författare)
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Placental immune response to apple allergen in allergic mothers
- 2014
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 106, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- The immunological milieu in the placenta may be crucial for priming the developing foetal immune system. Early imbalances may promote the establishment of immune-mediated diseases in later life, including allergies. The initial exposure to allergens seems to occur in utero, but little is known about allergen-induced placental cytokine and chemokine release. The release of several cytokines and chemokines from placenta tissue after exposure to mast cell degranulator compound 48/80 or apple allergen in placentas from allergic and healthy mothers was to be analysed. Four placentas from women with apple allergy and three controls were applied in a placental perfusion model with two separate cotyledons simultaneously perfused with and without apple allergen (Mal d 1). Two control placentas were perfused with compound 48/80. In outflow, histamine was quantified spectrophotofluorometrically, IL-2, IL-4, IL-6, IL-10, TNF and IFN-gamma by a cytometric multiplex bead array and IL-13 and CXCL10, CXCL11, CCL17 and CCL22 with an in-house multiplex Luminex assay. Compound 48/80 induced a rapid release of histamine, CXCL10, CXCL11, CCL17 and CCL22, but not of the other factors. Apple allergen induced a time-dependent release of IL-6 and TNF, but not of histamine, in placentas of women with apple allergy compared with the unstimulated cotyledon. CCL17 levels were slightly increased after allergen stimulation in control placentas. Allergens can induce placental cytokines and chemokines distinctly in allergic and healthy mothers. These mediators may affect the prenatal development of the immune system and modify the risk of diseases related to immune disorders in childhood such as allergies.
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| 9. |
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| 10. |
- Bartoszek, Krzysztof, et al.
(författare)
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Controversies around the statistical presentation of data on mRNA-COVID 19 vaccine safety in pregnant women
- 2022
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Ingår i: Journal of Reproductive Immunology. - : ELSEVIER IRELAND LTD. - 0165-0378 .- 1872-7603. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- The work entitled "Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons" published on April 21, 2021, in The New England Journal of Medicine, presented data collected from American surveillance systems and registries. However, problems with an unanimous interpretation of those results appeared in the public debate and citing articles. Some stated that the risk of miscarriage in vaccinated women was similar to historical values reported before the vaccines approval. The others stated that risk was highly above-normative in women vaccinated during the first and second trimesters. We found several problems with the statistical treatment/interpretation of the originally presented values: a substantial percentage (up to 95.6%) of missing data, an incorrect denominator used for risk estimation, and too short follow-up that disabled the evaluation of the studys endpoint in numerous participants. Eventually, the Authors published a corrigendum on September 8, 2021, and pointed to updated data. Herein, we explain the statistical controversies raised by the original presentation and stress that analyzing the trade-off between knowledge and confusion brought by the release of incomplete results of such a high social interest, should aid in solving the dilemma of whether to publish preliminary data or none.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Bruno, V., et al.
(författare)
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Low molecular weight heparin -induced miRNA changes in peripheral blood mononuclear cells in pregnancies with unexplained recurrent pregnancy loss
- 2022
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Ingår i: Journal of Reproductive Immunology. - : ELSEVIER IRELAND LTD. - 0165-0378 .- 1872-7603. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Unexplained recurrent pregnancy loss (uRPL) is a clinical condition for which there is a lack of evidenced-based therapies. However, in clinical practice, low molecular weight heparin (LMWH) has been widely used as an empirical therapy since immune effects have been hypothesized in modulating immune tolerance at the fetal maternal interface. Epigenetic mechanisms are involved in establishing of immune tolerance, at fetal-maternal interface. To investigate potential induced immune-epigenetic changes at maternal periphery level, which could reflect the maternal-fetal interface condition, seems to open up new therapeutical strategies, since microRNAs circulating in maternal plasma and in peripheral blood mononuclear cells (PBMCs) may be specific and sensitive immunological markers/predictors of adverse pregnancy outcomes such as RPL.Our aim in this pilot study is to evaluate potential LMWH effects on genes regulating immunological response key mechanisms related to maternal-fetal tolerance processes, by studying circulating miRNAs in maternal peripheral blood. We tested a panel of selected miRNAs on three groups: 18 healthy pregnant women, 20 pregnant women affected by uRPL, 18 pregnant women affected by uRPL, treated with LMWH. The majority of differentially expressed miRNAs (miR 374a-5p, 19a-3p, 30e-5p, 128-3p, 155-5p and 200c-3p) were found to be modulated by LMWH, which seems to have a positive function in RPL patients, by bringing patients values back to those comparable to the control ones. Selected microRNA panels would appear to be an effective clinical tool for uRPL diagnosis and management. LMWH-modified miRNA expression levels could be targets for immunotherapy, as LMWH would appear to restore physiological miRNA levels, which are dysregulated in uRPL.
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| 15. |
- Brännström, Mats, 1958, et al.
(författare)
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Leukocyte networks and ovulation.
- 2002
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Ingår i: Journal of reproductive immunology. - 0165-0378. ; 57:1-2, s. 47-60
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Tidskriftsartikel (refereegranskat)abstract
- Ovulation, the process whereby the oocyte is expelled from the interior of the follicle, is the final process of folliculogenesis. During the last decade, data have accumulated to suggest that tissue-bound leukocytes are major effector cells in several physiological processes within the reproductive tract. Some specific subclasses of leukocytes seem to be critically involved in the process of ovulation. The main components of this ovulatory process are degradation of the extracellular matrix (ECM) at the follicular apex and changes in the follicular vasculature. The leukocytes participate actively in these events by secretion of proteases and vasoactive substances. This review covers our current understanding of the mechanisms by which the leukocytes are attracted to the preovulatory follicle after the LH-surge and the roles that the activated leukocytes play in the follicle during the ovulatory period.
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| 16. |
- Collin, Mattias, et al.
(författare)
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Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract.
- 2008
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 79, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- The reproductive tract is continuously challenged by potential pathogens present in the environment. Therefore, robust host defense mechanisms are essential both for the health of the individual and for fertilization. Antibiotic innate immunity peptides possess broad antimicrobial activity. Recently, we found that the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses antibacterial activity. In the present study, we investigated, therefore, the presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors, i.e. at levels more than 100 times higher than those previously reported for the related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of healthy donors, indicating local production in the male reproductive tract. In vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean: 3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal vesicles, while the prostate epithelium showed weak expression, as determined by immunohistochemistry. A biological function is suggested, viz. at concentrations of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in seminal plasma may play roles in both host defense of the male urogenital tract and during fertilization.
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| 17. |
- Consiglio, Camila, et al.
(författare)
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Immune system adaptation during gender-affirming testosterone treatment
- 2023
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
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| 18. |
- Cunningham, Kelly A, et al.
(författare)
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CTA1-DD is an effective adjuvant for targeting anti-chlamydial immunity to the murine genital mucosa.
- 2009
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Ingår i: Journal of reproductive immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 81:1, s. 34-8
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is a significant human pathogen with potentially severe disease sequelae in the genital tract, including infertility. A successful vaccine will need to effectively target immunity to the genital mucosa. Intranasal immunisation with cholera toxin (CT) can target immunity to the genital tract, but has the potential to cause neurological side effects. CTA1-DD is a non-toxic potent mucosal adjuvant which combines the enzymatic properties of CT, with a B cell targeting moiety. Here, we demonstrate that intranasal immunisation with CTA1-DD and chlamydial Major Outer Membrane Protein (MOMP) results in the induction of neutralising systemic and mucosal antibodies, and reduces the level of chlamydial shedding following intravaginal challenge with Chlamydia muridarum. Thus, CTA1-DD is an effective adjuvant for vaccine development against Chlamydia trachomatis, and possibly also a range of other genital pathogens.
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| 19. |
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| 20. |
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| 21. |
- Dubicke, Aurelija, et al.
(författare)
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High-mobility group box protein 1 and its signalling receptors in human preterm and term cervix
- 2010
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 84:1, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to identify possible changes in mRNA and protein expression of high-mobility group box protein 1 (HMGB1) and its suggested receptors - receptor for advanced glycation end-products (RAGE) and Toll-like receptor 2 (TLR2) and TLR4 - in human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 58 women: 20 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. Real-time RT-PCR was used to quantify mRNA expression, and immunohistochemistry and ELISA for protein analysis. HMGB1, RAGE, TLR2 and TLR4 proteins were localized and their mRNA expression was detected in the cervix. There was more extranuclear HMGB1 in the cervical epithelium and stroma in preterm and term labor compared to the term not in labor. TLR2 mRNA expression was upregulated 5-fold in term labor and 3-fold in preterm labor compared to term not in labor and non-pregnant controls. There was lower expression of TLR2 and TLR4 mRNAs in preterm labor compared to term. Lower mRNA expression of HMGB1 was found in the subgroup with preterm premature rupture of membranes than in the rest of the preterm group, where levels were significantly higher than in term labor. In conclusion, extranuclear expression of HMGB1 during labor suggests a possible role of HMGB1 during the process of cervical ripening. Changes in expression of mRNAs encoding HMGB1, TLR2 and TLR4 in preterm labor suggest differences in the mechanism of cervical ripening at preterm and term delivery. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 22. |
- Dubicke, Aurelija, et al.
(författare)
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Pro-inflammatory and anti-inflammatory cytokines in human preterm and term cervical ripening
- 2010
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 84:2, s. 176-185
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Tidskriftsartikel (refereegranskat)abstract
- Cervical ripening is necessary for successful delivery. Since cytokines are believed to be involved in this process, the aim of this study was to investigate possible changes in the mRNA and protein expression of pro-inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-12, IL-18) and anti-inflammatory cytokines (IL-4, IL-10, IL-13)in the human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1 alpha and IL-1 beta in the laboring groups, while mRNA for IL-12 and IL-18 was downregulated. IL-4 mRNA was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor group than in the term labor group. The protein levels of IL-4 and IL-12 were lower and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial infection than in the non-infected group. IL-10 had higher expression in squamous epithelium at preterm labor than at term. In conclusion, the major changes in pro-inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur during the labor process irrespective of the length of gestation. Our results indicate that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in the pathogenesis of preterm labor.
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| 23. |
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| 24. |
- Forsberg, Anna, et al.
(författare)
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Plasticity and flexibility of T cells in human pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 149-149
- 2011
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Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY. - : Elsevier. - 0165-0378. ; , s. 149-149
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Konferensbidrag (refereegranskat)abstract
- Introduction:Pregnancy challenges the immune system. Thus, tolerance to the semi-allogenic fetus must be supported while the mother and fetus still must be protected against infectious agents. Pregnancy is associated with a Th2 deviated immune system, away from a harmful Th1 associated immunity, although this may be a simplified view. Regulatory T cells (Tregs) are enriched in the uterus, but occur at normal frequency in the circulation. It has become increasingly evident that Tregs and T helper cells are not stably committed lineages but are plastic, showing close relationships between subsets. We hypothesize that an increased T cell flexibility in pregnancy can help to explain the paradox of simultaneous tolerance and strong antimicrobial responses. Our aim was to investigate whether the plasticity concept is applicable for the Treg subset, and if it involves the entire T helper population. Material and methods: Isolated Tregs (CD4dimCD25high) and control cells (CD4+CD25−) from second trimester pregnant (n = 14) and non-pregnant women (n = 14) were stimulated for 24 h with plate-bound anti-CD3/anti-CD28. Signature gene and protein expression of each T cell subset was measured using transcription factor expression by real time-PCR and multiplex bead array of cell culture supernatants, respectively. The whole PBMC fraction is also used in ongoing experiments and either stimulated with plate-bound anti-CD3/anti-CD28 or with the Th1, Th2 and Th17 deviating microbial agents PPD (Th1), TT (Th2) and C. albicans hyphae (Th17). After culturing, the cells are stained for intracellular transcription factors associated with Th1, Th2, Th17 and Treg immunity. Results: Stimulated Tregs from pregnant compared to non-pregnant women showed significantly higher levels of markers for Treg cells (Foxp3 mRNA), Th2 cells (GATA-3 mRNA and IL4 protein) and a tendency to increase in markers of Th17 (RORC mRNA and IL-17 protein), whereas Th1 markers (Tbet mRNA and IFN-γ) showed no difference between pregnant and non-pregnant women. Further, ongoing studies may reveal if the entire T helper population shows a higher degree of responsiveness during pregnancy. Conclusions: Our results imply an increased plasticity of the Treg population during pregnancy, suggesting that Treg cells are able to switch to a Th2/Th17-like phenotype, depending on current demands of tolerance or infectious threats.
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| 25. |
- Gustafsson (Lidström), Charlotte, et al.
(författare)
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Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour : ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha
- 2006
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Ingår i: Journal of reproductive immunology. - : Elsevier BV. - 0165-0378. ; 71:1, s. 41-56
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10, transforming growth factor-β (TGF-β) and tumour necrosis factor-α (TNF-α) in decidual tissue with or without labour. Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n = 17) or after normal vaginal delivery (n = 15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES). Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-γ, IL-4, IL-10, TGF-β and TNF-α. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.
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