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Article ; Online: NK cell receptor profiling of endometrial and decidual NK cells reveals pregnancy-induced adaptations.

Feyaerts, Dorien / Benner, Marilen / Comitini, Gaia / Shadmanfar, Wijs / van der Heijden, Olivier W H / Joosten, Irma / van der Molen, Renate G

Frontiers in immunology

2024 Volume 15, Page(s) 1353556

Abstract: Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK ... ...

Abstract	Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK cells present during pregnancy. Microenvironmental changes can alter the phenotype of NK cells, but it is unclear whether decidual NK cell precursors in the endometrium alter their NK cell receptor repertoire under the influence of pregnancy. To examine whether decidual NK cell precursors reveal phenotypic modifications upon pregnancy, we immunophenotyped the NK cell receptor repertoire of both endometrial and early-pregnancy decidual NK cells using flow cytometry. We showed that NK cells in pre-pregnancy endometrium have a different phenotypic composition compared to NK cells in early-pregnancy decidua. The frequency of killer-immunoglobulin-like receptor (KIR expressing NK cells, especially KIR2DS1, KIR2DL2L3S2, and KIR2DL2S2 was significantly lower in decidua, while the frequency of NK cells expressing activating receptors NKG2D, NKp30, NKp46, and CD244 was significantly higher compared to endometrium. Furthermore, co-expression patterns showed a lower frequency of NK cells co-expressing KIR3DL1S1 and KIR2DL2L3S2 in decidua. Our results provide new insights into the adaptations in NK cell receptor repertoire composition that NK cells in the uterine mucosa undergo upon pregnancy.
MeSH term(s)	Pregnancy ; Female ; Humans ; Receptors, Natural Killer Cell ; Endometrium ; Killer Cells, Natural ; Uterus ; Mucous Membrane
Chemical Substances	Receptors, Natural Killer Cell
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1353556
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Article ; Online: Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies.

Mulder, Patrick P G / Hooijmans, Carlijn R / Vlig, Marcel / Middelkoop, Esther / Joosten, Irma / Koenen, Hans J P M / Boekema, Bouke K H L

The Journal of investigative dermatology

2023 Volume 144, Issue 3, Page(s) 669–696.e10

Abstract: Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related ... ...

Abstract	Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.
MeSH term(s)	Humans ; Rats ; Male ; Animals ; Interleukin-6 ; Inflammation Mediators ; Cytokines/metabolism ; Burns/metabolism ; Interleukin-1beta ; Inflammation ; Immunity
Chemical Substances	Interleukin-6 ; Inflammation Mediators ; Cytokines ; Interleukin-1beta
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.09.269
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Article ; Online: A pregnancy to remember: trained immunity of the uterine mucosae.

Feyaerts, Dorien / Joosten, Irma / van der Molen, Renate G

Mucosal immunology

2020 Volume 14, Issue 3, Page(s) 539–541

MeSH term(s)	Animals ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/immunology ; Female ; HLA-G Antigens/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Immunologic Memory ; Killer Cells, Natural/immunology ; Mice ; Models, Immunological ; Mucous Membrane/immunology ; Placentation ; Pregnancy/immunology ; Uterus/immunology ; HLA-E Antigens
Chemical Substances	HLA-G Antigens ; Histocompatibility Antigens Class I
Language	English
Publishing date	2020-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-020-00362-7
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Article ; Online: Burn-Induced Local and Systemic Immune Response: Systematic Review and Meta-Analysis of Animal Studies.

Mulder, Patrick P G / Koenen, Hans J P M / Vlig, Marcel / Joosten, Irma / de Vries, Rob B M / Boekema, Bouke K H L

The Journal of investigative dermatology

2022 Volume 142, Issue 11, Page(s) 3093–3109.e15

Abstract: Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, ...

Abstract	Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
MeSH term(s)	Rats ; Animals ; Burns/metabolism ; Neutrophils ; Macrophages/metabolism ; Anti-Bacterial Agents ; Inflammation Mediators/metabolism
Chemical Substances	Anti-Bacterial Agents ; Inflammation Mediators
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2022.05.004
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Article ; Online: N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma.

Langerhorst, Pieter / Baerenfaenger, Melissa / Kulkarni, Purva / Nadal, Simon / Wijnands, Charissa / Post, Merel A / Noori, Somayya / vanDuijn, Martijn M / Joosten, Irma / Dejoie, Thomas / van Gool, Alain J / Gloerich, Jolein / Lefeber, Dirk J / Wessels, Hans J C T / Jacobs, Joannes F M

Clinical chemistry and laboratory medicine

2024

Abstract: Objectives: Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent ... ...

Abstract	Objectives: Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity to provide a site-specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. Methods: Glycoproteogenomics was used for the detailed analysis of Results: Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to Fab Light Chain N-glycosylation of polyclonal antibodies from healthy individuals. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the Fab N-glycosylation sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. Conclusions: Together, glycoproteogenomics is a powerful tool to study
Language	English
Publishing date	2024-02-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-1189
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Article ; Online: Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4

Sengun, Ezgi / Wolfs, Tim G A M / van Bruggen, Valéry L E / van Cranenbroek, Bram / Simonetti, Elles R / Ophelders, Daan / de Jonge, Marien I / Joosten, Irma / van der Molen, Renate G

Frontiers in immunology

2023 Volume 14, Page(s) 1128359

Abstract: Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), ... ...

Abstract	Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), exert immunomodulatory effects and have regenerative capacity making it a promising therapeutic option for resolution of acute and chronic inflammation. T cells play a critical role in inflammation and depending on their phenotype, they can stimulate or suppress inflammatory responses. However, the regulatory effects of hMSC on T cells and the underlying mechanisms are not fully elucidated. Most studies focused on activation, proliferation, and differentiation of T cells. Here, we further investigated memory formation and responsiveness of CD4
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; Umbilical Cord ; CD4-Positive T-Lymphocytes ; Mesenchymal Stem Cells ; Inflammation ; Phenotype
Language	English
Publishing date	2023-06-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1128359
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Article ; Online: Monocytes and T cells incorporated in full skin equivalents to study innate or adaptive immune reactions after burn injury.

Mulder, Patrick P G / Vlig, Marcel / Elgersma, Anouk / Rozemeijer, Lotte / Mastenbroek, Leonore S / Middelkoop, Esther / Joosten, Irma / Koenen, Hans J P M / Boekema, Bouke K H L

Frontiers in immunology

2023 Volume 14, Page(s) 1264716

Abstract: Introduction: Thermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating the inflammatory processes following burn injuries, ... ...

Abstract	Introduction: Thermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating the inflammatory processes following burn injuries, thereby impeding the development of more effective therapies to improve burn wound healing in patients. Methods: In this study, we established a human full skin equivalent (FSE) burn wound model and incorporated human peripheral blood-derived monocytes and T cells. Results: Upon infiltration into the FSEs, the monocytes differentiated into macrophages within a span of 7 days. Burn-injured FSEs exhibited macrophages with increased expression of HLA-DR Discussion: Collectively, this study represents a significant advancement in the development of an immunocompetent human skin model, specifically tailored for investigating burn-induced innate or adaptive immune reactions at the site of burn injury.
MeSH term(s)	Humans ; Interleukin-8 ; Monocytes ; Cytokines ; Burns ; T-Lymphocyte Subsets
Chemical Substances	Interleukin-8 ; Cytokines
Language	English
Publishing date	2023-10-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1264716
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Article ; Online: Antibiotic Intervention Affects Maternal Immunity During Gestation in Mice.

Benner, Marilen / Lopez-Rincon, Alejandro / Thijssen, Suzan / Garssen, Johan / Ferwerda, Gerben / Joosten, Irma / van der Molen, Renate G / Hogenkamp, Astrid

Frontiers in immunology

2021 Volume 12, Page(s) 685742

Abstract: Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs ... ...

Abstract	Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs may interfere in these processes, they constitute the most frequently prescribed medication during pregnancy to prohibit detrimental consequences of infections. Gestational antibiotic intervention is linked to preeclampsia and negative effects on neonatal immunity. Even though perturbations in the immune system of the mother can affect reproductive health, the impact of microbial manipulation on maternal immunity is still unknown. Aim: To assess whether antibiotic treatment influences maternal immunity during pregnancy. Methods: Pregnant mice were treated with broad-spectrum antibiotics. The maternal gut microbiome was assessed. Numerous immune parameters throughout the maternal body, including placenta and amniotic fluid were investigated and a novel machine-learning ensemble strategy was used to identify immunological parameters that allow distinction between the control and antibiotic-treated group. Results: Antibiotic treatment reduced diversity of maternal microbiota, but litter sizes remained unaffected. Effects of antibiotic treatment on immunity reached as far as the placenta. Four immunological features were identified by recursive feature selection to contribute to the most robust classification (splenic T helper 17 cells and CD5 Conclusion: In the present study, antibiotic treatment was able to affect the carefully coordinated immunity during pregnancy. These findings highlight the importance of inclusion of immunological parameters when studying the effects of medication used during gestation.
MeSH term(s)	Adaptive Immunity/immunology ; Animals ; Animals, Newborn/immunology ; Animals, Newborn/microbiology ; Anti-Bacterial Agents/pharmacology ; Antibodies, Bacterial/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Female ; Gastrointestinal Microbiome/genetics ; Gastrointestinal Microbiome/immunology ; Immunoglobulin G/immunology ; Immunoglobulin M/immunology ; Intestines/microbiology ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pregnancy
Chemical Substances	Anti-Bacterial Agents ; Antibodies, Bacterial ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2021-08-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.685742
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Article ; Online: Immune responses to azacytidine in animal models of inflammatory disorders: a systematic review.

Landman, Sija / van der Horst, Chiel / van Erp, Piet E J / Joosten, Irma / de Vries, Rob / Koenen, Hans J P M

Journal of translational medicine

2021 Volume 19, Issue 1, Page(s) 11

Abstract: Inflammatory disorders like diabetes, systemic lupus erythematodes, inflammatory lung diseases, rheumatoid arthritis and multiple sclerosis, but also rejection of transplanted organs and GvHD, form a major burden of disease. Current classes of immune ... ...

Abstract	Inflammatory disorders like diabetes, systemic lupus erythematodes, inflammatory lung diseases, rheumatoid arthritis and multiple sclerosis, but also rejection of transplanted organs and GvHD, form a major burden of disease. Current classes of immune suppressive drugs to treat these disorders are never curative and side effects are common. Therefore there is a need for new drugs with improved and more targeted modes of action. Potential candidates are the DNA methyl transferase inhibitor 5-azacytidine (Aza) and its derivative 5-aza 2'deoxycitidine (DAC). Aza and DAC have been tested in several pre-clinical in vivo studies. In order to obtain an overview of disorders for which Aza and/or DAC can be a potential treatment, and to find out where information is lacking, we systematically reviewed pre-clinical animal studies assessing Aza or DAC as a potential therapy for distinct inflammatory disorders. Also, study quality and risk of bias was systematically assessed. In the 35 identified studies, we show that both Aza and DAC do not only seem to be able to alleviate a number of inflammatory disorders, but also prevent solid organ rejection and GvHD in in vivo pre-clinical animal models. Aza/DAC are known to upregulate FOXP3, a master transcription factor for Treg, in vitro. Seventeen studies described the effect on Treg, of which 16 studies showed an increase in Treg. Increasing Treg therefore seems to be a common mechanism in preventing inflammatory disorders by Aza/DAC. We also found, however, that many essential methodological details were poorly reported leading to an unclear risk of bias. Therefore, reported effects might be an overestimation of the true effect.
MeSH term(s)	Animals ; Azacitidine/pharmacology ; Azacitidine/therapeutic use ; Decitabine ; Immunity ; Models, Animal ; T-Lymphocytes, Regulatory
Chemical Substances	Decitabine (776B62CQ27) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-020-02615-2
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Article ; Online: Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction.

van Beek, Lucille F / Welzen, Pascal L W / Teufel, Lisa U / Joosten, Irma / Diavatopoulos, Dimitri A / van Hest, Jan / de Jonge, Marien I

Biomacromolecules

2021 Volume 22, Issue 10, Page(s) 4422–4433

Abstract: The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient ... ...

Abstract	The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient interaction with and activation of cells involved in antigen presentation, which can be achieved by targeting cellular receptors. Here, we showed that the Fc fragment display on the polymersome surface resulted in markedly improved interactions with granulocytes, monocytes, and NK cells, while for "naked" polymersomes, virtually no binding to leukocytes was observed. Moreover, CpG-decorated polymersomes were found to also interact with T and/or B cells. Interestingly, whole blood stimulations with Fc fragment and CpG-decorated polymersomes induced interleukin (IL)-6, IL-8, and TNF-α production, while naked polymersomes did not induce any cytokine production. In conclusion, specific immune induction by polymersomes can be controlled using bimodal targeting of different immune receptors, which is an essential feature for targeted vaccine delivery.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Drug Delivery Systems ; Humans ; Leukocytes ; Nanoparticles ; Polymers
Chemical Substances	Adjuvants, Immunologic ; Polymers
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.1c00985
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