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BETA
Berg, Göran
Alternative names
Publications (10 of 70) Show all publications
Svensson Arvelund, J., Söderberg, D., Wendel, C., Freland, S., Geffers, R., Berg, G., . . . Ernerudh, J. (2015). Decidual macrophages contribute to the unique leukocyte composition at the fetal-maternal interface by production of IL-35, induction of Treg cells and production of homeostatic chemokines.
Open this publication in new window or tab >>Decidual macrophages contribute to the unique leukocyte composition at the fetal-maternal interface by production of IL-35, induction of Treg cells and production of homeostatic chemokines
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2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Reproductive success depends on the ability of the maternal immune system to adapt in order to tolerate and support the growing semi-allogenic fetus. Macrophages, being a major leukocyte population in the uterine mucosa (decidua), may play a central role in promoting the unique composition and regulatory phenotype of leukocytes that is characteristic for the fetal-maternal interface. We show that decidual macrophages display a predominantly immune regulatory gene profile and produce the immunosuppressive cytokine IL-35 but no other members of the IL-12 family (IL-12, IL-23 and IL-27). Decidual macrophages also promoted the selective expansion of CD25highFoxp3+ Tregs but not of Tbet+ Th1, GATA-3+ Th2 and Rorγt+ Th17 cells. In addition, these macrophages preferentially secreted the monocyte- and Treg-associated chemokines CCL2 and CCL18, while Th1-, Th2- and Th17-related chemokines were produced at low levels. Among in vitro macrophages, distinct chemokine profiles were observed; IL-4/13 upregulated Th2-associated chemokines (CCL17, CCL22, CCL26) while LPS/IFNγ upregulated Th1-associated chemokines (CXCL9, CXCL10, CXCL11, CCL5). M(IL-10) macrophages (induced by M-CSF and IL-10) showed a chemokine profile similar to that of decidual macrophages, as shown by gene expression and protein analysis. By using M(IL-10) macrophages as a model of decidual macrophages, we show that these cells promote the recruitment of CD14+ monocytes, while migration of several lymphocyte populations was unaltered or prevented. These data implicate decidual macrophages as critical regulators of the decidual leukocyte composition and phenotype that is associated with successful reproduction.

National Category
Immunology Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117182 (URN)
Available from: 2015-04-21 Created: 2015-04-21 Last updated: 2018-07-18Bibliographically approved
Christmann, B. S., Abrahamsson, T., Bernstein, C. N., Wayne Duck, L., Mannon, P. J., Berg, G., . . . Elson, C. O. (2015). Human seroreactivity to gut microbiota antigens. Journal of Allergy and Clinical Immunology, 136(5), 1378-1386
Open this publication in new window or tab >>Human seroreactivity to gut microbiota antigens
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2015 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 136, no 5, p. 1378-1386Article in journal (Refereed) Published
Abstract [en]

Background: Although immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective: Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response with the response observed in 52 children and their mothers at risk of having allergic disease. Methods: Human serum was collected from adults and children followed from birth to 7 years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed by using a novel protein microarray. Results: Nearly every subject tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions: There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic subjects. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota might be needed to prevent certain immune-mediated diseases.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2015
Keywords
Adaptive; atopy; allergy; childhood; IgG; microarray; microbiota; bacterial antigens; bacterial antibodies
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123148 (URN)10.1016/j.jaci.2015.03.036 (DOI)000364787200028 ()26014812 (PubMedID)
Note

Funding Agencies|National Institutes of Health [DK071176]; Swedish Research Council [K2011-56X-21854-01-06]; Swedish Heart-Lung Foundation [20050514]; Ekhaga Foundation [210-53]; Research Council for the South-East Sweden; Olle Engqvist Foundation; Swedish Asthma and Allergy Association; Vardal Foundation for Health Care Science and Allergy Research, Sweden [B2007 042]; University Hospital of Linkoping, Sweden

Available from: 2015-12-07 Created: 2015-12-04 Last updated: 2017-12-01
Boij, R., Mjosberg, J., Svensson Arvelund, J., Hjorth, M., Berg, G., Matthiesen, L., . . . Ernerudh, J. (2015). Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia. American Journal of Reproductive Immunology, 74(4), 368-378
Open this publication in new window or tab >>Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
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2015 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 4, p. 368-378Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
Keywords
Early-onset preeclampsia; preeclampsia; pregnancy; regulatory T cells
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-122528 (URN)10.1111/aji.12410 (DOI)000362664200009 ()26118401 (PubMedID)
Note

Funding Agencies|FORSS (Medical Research Council of Southeast Sweden); Futurum, academy for Health and Care Jonkoping County Council, Sweden

Available from: 2015-11-09 Created: 2015-11-06 Last updated: 2017-12-01
Svensson, J., Bhai Mehta, R., Lindau, R., Mirrasekhian, E., Rodriguez-Martinez, H., Berg, G., . . . Ernerudh, J. (2015). The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages. Journal of Immunology, 194(4), 1534-1544
Open this publication in new window or tab >>The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages
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2015 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 194, no 4, p. 1534-1544Article in journal (Refereed) Published
Abstract [en]

A successful pregnancy requires that the maternal immune system is instructed to a state of tolerance to avoid rejection of the semiallogeneic fetal-placental unit. Although increasing evidence supports that decidual (uterine) macrophages and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not known how these tolerogenic leukocytes are induced. In this article, we show that the human fetal placenta itself, mainly through trophoblast cells, is able to induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10 induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23. Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs in parallel with increased IL-10 production, whereas production of IFN-gamma (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the suppressive markers CTLA-4 and CD39, were functionally suppressive, and were induced, in part, by IL-10, TGF-beta, and TRAIL. Placental-derived factors also limited excessive Th cell activation, as shown by decreased HLA-DR expression and reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data indicate that the fetal placenta has a central role in promoting the homeostatic environment necessary for successful pregnancy. These findings have implications for immune-mediated pregnancy complications, as well as for our general understanding of tissue-induced tolerance.

Place, publisher, year, edition, pages
American Association of Immunologists, 2015
National Category
Clinical Medicine Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-115319 (URN)10.4049/jimmunol.1401536 (DOI)000349462000017 ()25560409 (PubMedID)
Note

Funding Agencies|Medical Research Council [K2013-61X-22310-01-4]

Available from: 2015-03-13 Created: 2015-03-13 Last updated: 2018-01-11
Abelius, M. S., Janefjord, C., Ernerudh, J., Berg, G., Matthiesen, L., Duchén, K., . . . Jenmalm, M. (2015). The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity. American Journal of Reproductive Immunology, 73(5), 445-459
Open this publication in new window or tab >>The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity
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2015 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, no 5, p. 445-459Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
National Category
Clinical Medicine Cell and Molecular Biology Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-114069 (URN)10.1111/aji.12350 (DOI)000352810200007 ()25491384 (PubMedID)
Available from: 2015-02-06 Created: 2015-02-06 Last updated: 2018-01-11
Abelius, M. S., Janefjord, C., Ernerudh, J., Berg, G., Matthiesen, L., Duchén, K., . . . Jenmalm, M. (2014). Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women.
Open this publication in new window or tab >>Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106219 (URN)
Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2015-03-25Bibliographically approved
Abelius, M. S., Lempinen, E., Lindblad, K., Ernerudh, J., Berg, G., Matthiesen, L., . . . Jenmalm, M. (2014). Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy. Pediatric Allergy and Immunology, 25(4), 387-393
Open this publication in new window or tab >>Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy
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2014 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, p. 387-393Article in journal (Refereed) Published
Abstract [en]

Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
Keywords
Allergy; CCL17; CCL22; chemokines; pregnancy; Th2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106218 (URN)10.1111/pai.12235 (DOI)000338037100013 ()
Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2017-12-05Bibliographically approved
Kalkunte, S. S., Neubeck, S., Norris, W. E., Cheng, S.-B., Kostadinov, S., Hoang, D. V., . . . Sharma, S. (2013). Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model. American Journal of Pathology, 183(5), 1425-1436
Open this publication in new window or tab >>Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model
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2013 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 183, no 5, p. 1425-1436Article in journal (Refereed) Published
Abstract [en]

Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinal, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102082 (URN)10.1016/j.ajpath.2013.07.022 (DOI)000326553400010 ()
Note

Funding Agencies|NIH|P20RR018728|National Institute of Environmental Health Sciences|P42ES013660|Rhode Island Research Alliance Collaborative Research Award|2009-28|

Available from: 2013-12-02 Created: 2013-11-29 Last updated: 2017-12-06
Boij, R., Svensson, J., Nilsson-Ekdahl, K., Sandholm, K., Lindahl, T., Palonek, E., . . . Matthiesen, L. (2012). Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia. AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 68(3), 258-270
Open this publication in new window or tab >>Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
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2012 (English)In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, no 3, p. 258-270Article in journal (Refereed) Published
Abstract [en]

Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

Place, publisher, year, edition, pages
John Wiley and Sons, 2012
Keywords
preeclampsia, coagulation, inflammation, angiogenesis, chemokines, cytokines and early onset preeclampsia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81815 (URN)10.1111/j.1600-0897.2012.01158.x (DOI)000307440300012 ()
Note

Funding Agencies|FORSS (Medical Research Council of Southeast Sweden)||Futurum (the Research department of County of Jonkoping)||Swedish Research Council|2007-15809-48800-58|Linneaus University (Sweden)||

Available from: 2012-09-26 Created: 2012-09-24 Last updated: 2016-11-11
Boij, R., Berg, G., Nilsson-Ekdahl, K., Svensson, J., Sandholm, K., Lindahl, T., . . . Jarle, M. (2012). Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-109. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 109-109). Elsevier, 94(1)
Open this publication in new window or tab >>Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-109
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2012 (English)In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, no 1, p. 109-109Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-78578 (URN)10.1016/j.jri.2012.03.447 (DOI)000304579400201 ()
Available from: 2012-06-15 Created: 2012-06-15 Last updated: 2012-06-15
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