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  1. Article ; Online: Toward a bona fide animal model of PLA2R1-associated membranous nephropathy: one step forward.

    Bihl, Franck / Lambeau, Gérard

    Kidney international

    2023  Volume 103, Issue 2, Page(s) 251–253

    Abstract: The major form of membranous nephropathy is characterized by autoantibodies to phospholipase A2 receptor 1 (PLA2R1). The study by Tomas et al. describes the first animal model where human PLA2R1 is ectopically expressed in mouse podocytes. Intriguingly, ... ...

    Abstract The major form of membranous nephropathy is characterized by autoantibodies to phospholipase A2 receptor 1 (PLA2R1). The study by Tomas et al. describes the first animal model where human PLA2R1 is ectopically expressed in mouse podocytes. Intriguingly, the transgenic mice spontaneously develop anti-human PLA2R1 antibodies and membranous nephropathy-like features, including immune deposits and nephrotic syndrome. The model raises questions about the spontaneous production of anti-human PLA2R1 antibodies and the additional steps to establish a bona fide animal model of membranous nephropathy.
    MeSH term(s) Humans ; Animals ; Mice ; Glomerulonephritis, Membranous/genetics ; Receptors, Phospholipase A2/genetics ; Nephrotic Syndrome ; Podocytes ; Models, Animal ; Autoantibodies
    Chemical Substances Receptors, Phospholipase A2 ; Autoantibodies ; PLA2R1 protein, human
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.10.020
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  2. Article: What do secreted phospholipases A2 have to offer in combat against different viruses up to SARS-CoV-2?

    Pungerčar, Jože / Bihl, Franck / Lambeau, Gérard / Križaj, Igor

    Biochimie. 2021 Oct., v. 189

    2021  

    Abstract: Secreted phospholipases A₂ (sPLA₂s) form a widespread group of structurally-related enzymes that catalyse the hydrolysis of the sn-2 ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. In humans, nine catalytically ... ...

    Abstract Secreted phospholipases A₂ (sPLA₂s) form a widespread group of structurally-related enzymes that catalyse the hydrolysis of the sn-2 ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. In humans, nine catalytically active and two inactive sPLA₂ proteins have been identified. These enzymes play diverse biological roles, including host defence against bacteria, parasites and viruses. Several of these endogenous sPLA₂s may play a defensive role in viral infections, as they display in vitro antiviral activity by both direct and indirect mechanisms. However, endogenous sPLA₂s may also exert an offensive and negative role, dampening the antiviral response or promoting inflammation in animal models of viral infection. Similarly, several exogenous sPLA₂s, most of them from snake venoms and other animal venoms, possess in vitro antiviral activities. Thus, both endogenous and exogenous sPLA₂s may be exploited for the development of new antiviral substances or as therapeutic targets for antagonistic drugs that may promote a more robust antiviral response. In this review, the antiviral versus proviral role of both endogenous and exogenous sPLA₂s against various viruses including coronaviruses is presented. Based on the highlighted developments in this area of research, possible directions of future investigation are envisaged. One of them is also a possibility of exploiting sPLA₂s as biological markers of the severity of the Covid-19 pandemic caused by SARS-CoV-2 infection.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; glycerophospholipids ; hydrolysis ; inflammation ; lysophospholipids ; phospholipases ; snakes ; therapeutics
    Language English
    Dates of publication 2021-10
    Size p. 40-50.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 120345-9
    ISSN 0300-9084
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2021.05.017
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  3. Article ; Online: What do secreted phospholipases A

    Pungerčar, Jože / Bihl, Franck / Lambeau, Gérard / Križaj, Igor

    Biochimie

    2021  Volume 189, Page(s) 40–50

    Abstract: Secreted phospholipases ... ...

    Abstract Secreted phospholipases A
    MeSH term(s) Animals ; Antiviral Agents/therapeutic use ; COVID-19/enzymology ; COVID-19/epidemiology ; COVID-19/pathology ; Disease Models, Animal ; Humans ; Pandemics ; Phospholipases A2, Secretory/metabolism ; SARS-CoV-2/metabolism ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Phospholipases A2, Secretory (EC 3.1.1.4)
    Language English
    Publishing date 2021-06-16
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2021.05.017
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  4. Article: Role of human group IIA secreted phospholipase A2 in malaria pathophysiology: Insights from a transgenic mouse model

    Dacheux, Mélanie / Chaouch, Soraya / Joy, Alonso / Labat, Amandine / Payré, Christine / Petit-Paitel, Agnès / Bihl, Franck / Lagrange, Isabelle / Grellier, Philippe / Touqui, Lhousseine / Lambeau, Gérard / Deregnaucourt, Christiane

    Biochimie. 2021 Oct., v. 189

    2021  

    Abstract: We previously showed that injection of recombinant human group IIA secreted phospholipase A₂ (hGIIA sPLA₂) to Plasmodium chabaudi-infected mice lowers parasitaemia by 20%. Here, we show that transgenic (TG) mice overexpressing hGIIA sPLA₂ have a peak of ... ...

    Abstract We previously showed that injection of recombinant human group IIA secreted phospholipase A₂ (hGIIA sPLA₂) to Plasmodium chabaudi-infected mice lowers parasitaemia by 20%. Here, we show that transgenic (TG) mice overexpressing hGIIA sPLA₂ have a peak of parasitaemia about 30% lower than WT littermates. During infection, levels of circulating sPLA₂, enzymatic activity and plasma lipid peroxidation were maximal at day-14, the peak of parasitaemia. Levels of hGIIA mRNA increased in liver but not in spleen and blood cells, suggesting that liver may contribute as a source of circulating hGIIA sPLA₂. Before infection, baseline levels of leukocytes and pro-inflammatory cytokines were higher in TG mice than WT littermates. Upon infection, the number of neutrophils, lymphocytes and monocytes increased and were maximal at the peak of parasitaemia in both WT and TG mice, but were higher in TG mice. Similarly, levels of the Th1 cytokines IFN-γ and IL-2 increased in WT and TG mice, but were 7.7- and 1.7-fold higher in TG mice. The characteristic shift towards Th2 cytokines was observed during infection in both WT and TG mice, with increased levels of IL-10 and IL-4 at day-14. The current data are in accordance with our previous in vitro findings showing that hGIIA kills parasites by releasing toxic lipids from oxidized lipoproteins. They further show that hGIIA sPLA₂ is induced during mouse experimental malaria and has a protective in vivo role, lowering parasitaemia by likely releasing toxic lipids from oxidized lipoproteins but also indirectly by promoting a more sustained innate immune response.
    Keywords Plasmodium ; blood lipids ; enzyme activity ; humans ; innate immunity ; interleukin-10 ; interleukin-2 ; interleukin-4 ; lipid peroxidation ; lipoproteins ; liver ; malaria ; mice ; monocytes ; neutrophils ; oxidation ; parasitemia ; pathophysiology ; phospholipase A2 ; phospholipases ; spleen ; toxicity
    Language English
    Dates of publication 2021-10
    Size p. 120-136.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 120345-9
    ISSN 0300-9084
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2021.06.009
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  5. Article ; Online: Generation of a conditional transgenic mouse model expressing human Phospholipase A2 Receptor 1.

    Jaber, Sara / Goehrig, Delphine / Bertolino, Philippe / Massemin, Amélie / Bihl, Franck / Chabry, Joëlle / Lambeau, Gérard / Vindrieux, David / Bernard, David

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 8190

    Abstract: The Phospholipase A2 Receptor 1 (PLA2R1) was first identified for its ability to bind some secreted PLA2s (sPLA2s). It belongs to the C-type lectin superfamily and it binds different types of proteins. It is likely a multifunctional protein that plays a ... ...

    Abstract The Phospholipase A2 Receptor 1 (PLA2R1) was first identified for its ability to bind some secreted PLA2s (sPLA2s). It belongs to the C-type lectin superfamily and it binds different types of proteins. It is likely a multifunctional protein that plays a role i) in inflammation and inflammatory diseases, ii) in cellular senescence, a mechanism participating in aging and age-related diseases including cancer, and iii) in membranous nephropathy (MN), a rare autoimmune kidney disease where PLA2R1 is the major autoantigen. To help study the role of PLA2R1 in these pathophysiological conditions, we have generated a versatile NeoR-hPLA2R1 conditional transgenic mice which will allow the specific expression of human PLA2R1 (hPLA2R1) in relevant organs and cells following Cre recombinase-driven excision of the NeoR-stop cassette flanked by LoxP sites. Proof-of-concept breeding of NeoR-hPLA2R1 mice with the ubiquitous adenoviral EIIa promoter-driven Cre mouse line resulted in the expected excision of the NeoR-stop cassette and the expression of hPLA2R1 in all tested tissues. These Tg-hPLA2R1 animals breed normally, with no reproduction or apparent growth defect. These models, especially the NeoR-hPLA2R1 conditional transgenic mouse line, will facilitate the future investigation of PLA2R1 functions in relevant pathophysiological contexts, including inflammatory diseases, age-related diseases and MN.
    MeSH term(s) Animals ; Disease Models, Animal ; Gene Expression ; Genotyping Techniques ; Humans ; Mice ; Mice, Transgenic ; Organ Specificity ; Receptors, Phospholipase A2/genetics
    Chemical Substances PLA2R1 protein, human ; Receptors, Phospholipase A2
    Language English
    Publishing date 2020-05-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-64863-y
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  6. Article ; Online: Role of human group IIA secreted phospholipase A2 in malaria pathophysiology: Insights from a transgenic mouse model.

    Dacheux, Mélanie / Chaouch, Soraya / Joy, Alonso / Labat, Amandine / Payré, Christine / Petit-Paitel, Agnès / Bihl, Franck / Lagrange, Isabelle / Grellier, Philippe / Touqui, Lhousseine / Lambeau, Gérard / Deregnaucourt, Christiane

    Biochimie

    2021  Volume 189, Page(s) 120–136

    Abstract: We previously showed that injection of recombinant human group IIA secreted phospholipase ... ...

    Abstract We previously showed that injection of recombinant human group IIA secreted phospholipase A
    MeSH term(s) Animals ; Cytokines/genetics ; Cytokines/immunology ; Group II Phospholipases A2/genetics ; Group II Phospholipases A2/immunology ; Humans ; Malaria/genetics ; Malaria/immunology ; Mice ; Mice, Transgenic ; Plasmodium chabaudi/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology
    Chemical Substances Cytokines ; Group II Phospholipases A2 (EC 3.1.1.4) ; PLA2G2A protein, human (EC 3.1.1.4)
    Language English
    Publishing date 2021-06-24
    Publishing country France
    Document type Journal Article
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2021.06.009
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  7. Article: Cell biology and immunology of Leishmania

    Mougneau, Evelyne / Bihl, Franck / Glaichenhaus, Nicolas

    Immunological reviews. 2011 Mar., v. 240, no. 1

    2011  

    Abstract: Summary: More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune ... ...

    Abstract Summary: More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (IL-12) and IL-4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T-cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the early events that shape the immune response to Leishmania and on the immune evasion mechanisms that allow this parasite to avoid the development of sterilizing immunity and to secure its transmission to a new host.
    Language English
    Dates of publication 2011-03
    Size p. 286-296.
    Publishing place Blackwell Publishing Ltd
    Document type Article
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065X.2010.00983.x
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  8. Article: Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development.

    Khou, Sokchea / Popa, Alexandra / Luci, Carmelo / Bihl, Franck / Meghraoui-Kheddar, Aida / Bourdely, Pierre / Salavagione, Emie / Cosson, Estelle / Rubod, Alain / Cazareth, Julie / Barbry, Pascal / Mari, Bernard / Rezzonico, Roger / Anjuère, Fabienne / Braud, Veronique M

    Cancers

    2020  Volume 12, Issue 7

    Abstract: Cutaneous squamous cell carcinoma (cSCC) development has been linked to immune dysfunctions but the mechanisms are still unclear. Here, we report a progressive infiltration of tumor-associated neutrophils (TANs) in precancerous and established cSCC ... ...

    Abstract Cutaneous squamous cell carcinoma (cSCC) development has been linked to immune dysfunctions but the mechanisms are still unclear. Here, we report a progressive infiltration of tumor-associated neutrophils (TANs) in precancerous and established cSCC lesions from chemically induced skin carcinogenesis. Comparative in-depth gene expression analyses identified a predominant protumor gene expression signature of TANs in lesions compared to their respective surrounding skin. In addition, in vivo depletion of neutrophils delayed tumor growth and significantly increased the frequency of proliferating IFN-γ (interferon-γ)-producing CD8+ T cells. Mechanisms that limited antitumor responses involved high arginase activity, production of reactive oxygen species (ROS) and nitrite (NO), and the expression of programmed death-ligand 1 (PD-L1) on TAN, concomitantly with an induction of PD-1 on CD8
    Language English
    Publishing date 2020-07-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12071860
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  9. Article ; Online: Cell biology and immunology of Leishmania.

    Mougneau, Evelyne / Bihl, Franck / Glaichenhaus, Nicolas

    Immunological reviews

    2011  Volume 240, Issue 1, Page(s) 286–296

    Abstract: More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, ... ...

    Abstract More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (IL-12) and IL-4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T-cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the early events that shape the immune response to Leishmania and on the immune evasion mechanisms that allow this parasite to avoid the development of sterilizing immunity and to secure its transmission to a new host.
    MeSH term(s) Animals ; Cell Differentiation ; Cytokines/metabolism ; Humans ; Immune Evasion ; Immunity ; Leishmania major/immunology ; Leishmaniasis/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2011-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065X.2010.00983.x
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  10. Article ; Online: Cutaneous Squamous Cell Carcinoma Development Is Associated with a Temporal Infiltration of ILC1 and NK Cells with Immune Dysfunctions.

    Luci, Carmelo / Bihl, Franck / Bourdely, Pierre / Khou, Sokchea / Popa, Alexandra / Meghraoui-Kheddar, Aida / Vermeulen, Ophelie / Elaldi, Roxane / Poissonnet, Gilles / Sudaka, Anne / Bozec, Alexandre / Bekri, Selma / Cazareth, Julie / Ponzio, Gilles / Barbry, Pascal / Rezzonico, Roger / Mari, Bernard / Braud, Veronique M / Anjuère, Fabienne

    The Journal of investigative dermatology

    2021  Volume 141, Issue 10, Page(s) 2369–2379

    Abstract: NK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined ... ...

    Abstract NK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined transcriptomic and immunophenotyping analyses in mouse and human cSCCs. We identified an infiltration of NK cells and ILC1s as well as the presence of a few ILC3s. Adoptive transfer of NK cells in NK cell‒ and ILC-deficient Nfil3
    MeSH term(s) Adoptive Transfer ; Animals ; Basic-Leucine Zipper Transcription Factors/physiology ; Carcinoma, Squamous Cell/etiology ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/pathology ; Humans ; Immunity, Innate ; Killer Cells, Natural/immunology ; Killer Cells, Natural/physiology ; Lymphocytes/immunology ; Lymphocytes/physiology ; Mice ; Natural Cytotoxicity Triggering Receptor 1/analysis ; Neoplasm Staging ; Skin Neoplasms/etiology ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology
    Chemical Substances Basic-Leucine Zipper Transcription Factors ; NCR1 protein, human ; Natural Cytotoxicity Triggering Receptor 1 ; Nfil3 protein, mouse
    Language English
    Publishing date 2021-04-05
    Publishing country United States
    Document type 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.2021.03.018
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