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  1. Article ; Online: JAK/STAT: Why choose a classical or an alternative pathway when you can have both?

    Puigdevall, Léna / Michiels, Camille / Stewardson, Clara / Dumoutier, Laure

    Journal of cellular and molecular medicine

    2022  Volume 26, Issue 7, Page(s) 1865–1875

    Abstract: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as the induction of inflammation and immune responses. The receptors for these cytokines are dimers/trimers of transmembrane proteins devoid of intracellular kinase ... ...

    Abstract A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as the induction of inflammation and immune responses. The receptors for these cytokines are dimers/trimers of transmembrane proteins devoid of intracellular kinase activity. Instead, they rely on Janus kinases (JAKs) for signal transduction. Classical JAK-STAT signalling involves phosphorylation of cytokine receptors' intracellular tyrosines, which subsequently serve as docking sites for the recruitment and activation of STATs. However, there is evidence to show that several cytokine receptors also use a noncanonical, receptor tyrosine-independent path to induce activation of STAT proteins. We identified two main alternative modes of STAT activation. The first involves an association between a tyrosine-free region of the cytokine receptor and STATs, while the second seems to depend on a direct interaction between JAK and STAT proteins. We were able to identify the use of noncanonical mechanisms by almost a dozen cytokine receptors, suggesting they have some importance. These alternative pathways and the receptors that employ them are discussed in this review.
    MeSH term(s) Janus Kinases/genetics ; Janus Kinases/metabolism ; Phosphorylation ; Receptors, Cytokine/genetics ; Receptors, Cytokine/metabolism ; STAT Transcription Factors/genetics ; STAT Transcription Factors/metabolism ; Signal Transduction/physiology
    Chemical Substances Receptors, Cytokine ; STAT Transcription Factors ; Janus Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2022-03-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.17168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice.

    Gaignage, Mélanie / Zhang, Xuhao / Stockis, Julie / Dedobbeleer, Olivier / Michiels, Camille / Cochez, Perrine / Dumoutier, Laure / Coulie, Pierre G / Lucas, Sophie

    Cancer immunology, immunotherapy : CII

    2022  Volume 71, Issue 8, Page(s) 1851–1862

    Abstract: Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs ... ...

    Abstract Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of T
    MeSH term(s) Adaptive Immunity ; Animals ; Antibodies, Monoclonal/metabolism ; Bacterial Infections/immunology ; Bacterial Infections/metabolism ; Immunity ; Immunization ; Membrane Proteins/metabolism ; Mice ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta1/metabolism
    Chemical Substances Antibodies, Monoclonal ; Lrrc32 protein, mouse ; Membrane Proteins ; Transforming Growth Factor beta1
    Language English
    Publishing date 2022-01-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-021-03119-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Keratinocytes activated by IL-4/IL-13 express IL-2Rγ with consequences on epidermal barrier function.

    Progneaux, Audrey / Evrard, Céline / De Glas, Valérie / Fontaine, Alix / Dotreppe, Céline / De Vuyst, Evelyne / Nikkels, Arjen F / García-González, Vicente / Dumoutier, Laure / Lambert de Rouvroit, Catherine / Poumay, Yves

    Experimental dermatology

    2023  Volume 32, Issue 5, Page(s) 660–670

    Abstract: Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that ... ...

    Abstract Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that forms type I receptor for IL-4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role. We studied expression of IL-2Rγ in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL-2Rγ expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL-4/IL-13 and AD skin. IL-2Rγ induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL-2Rγ function was investigated in RHE KO for IL2RG. In RHE, IL-4/IL-13 induce expression of IL-2Rγ at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL-2Rγ expression is low in RHE treated with JAK inhibitors and absent in RHE KO for IL13RA1. Exposure to IL-4/IL-13 alters epidermal barrier, but this alteration is absent in RHE KO for IL2RG. A more important induction of IL-13Rα2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL-2Rγ induction in keratinocytes through activation of type II receptor. IL-2Rγ is involved in the alteration of the epidermal barrier and in the regulation of IL-13Rα2 expression. Observation of IL-2Rγ expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease.
    MeSH term(s) Humans ; Cells, Cultured ; Dermatitis, Atopic/metabolism ; Epidermis/metabolism ; Interleukin-13/metabolism ; Interleukin-4/metabolism ; Janus Kinase Inhibitors ; Keratinocytes/metabolism ; RNA, Messenger/metabolism ; Interleukin Receptor Common gamma Subunit/metabolism
    Chemical Substances Interleukin-13 ; Interleukin-4 (207137-56-2) ; Janus Kinase Inhibitors ; RNA, Messenger ; IL2RG protein, human ; Interleukin Receptor Common gamma Subunit
    Language English
    Publishing date 2023-01-26
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 1130936-2
    ISSN 1600-0625 ; 0906-6705
    ISSN (online) 1600-0625
    ISSN 0906-6705
    DOI 10.1111/exd.14749
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

    Michiels, Camille / Puigdevall, Léna / Cochez, Perrine / Achouri, Younes / Cheou, Paméla / Hendrickx, Emilie / Dauguet, Nicolas / Blanchetot, Christophe / Dumoutier, Laure

    The Journal of investigative dermatology

    2021  Volume 141, Issue 11, Page(s) 2668–2678.e6

    Abstract: Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of ... ...

    Abstract Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed in vitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Rα) Y-dependent and -independent pathways. The second depends on the C-terminal Y-less region of IL-22Rα and leads to a massive signal transducer and activator of transcription 3 (STAT3) activation. Because STAT3 activation is associated with the development of psoriasis, we hypothesized that the specific inhibition of the noncanonical STAT3 activation by the Y-less region of IL-22Rα could reduce psoriasis-like disease while leaving intact its tissue defense functions in the gut. We show that mice expressing a C-terminally truncated version of IL-22Rα (ΔCter
    MeSH term(s) Animals ; Citrobacter rodentium ; Enterobacteriaceae Infections/immunology ; Imiquimod/toxicity ; Interleukins/pharmacology ; Mice ; Mice, Inbred C57BL ; Psoriasis/chemically induced ; Receptors, Interleukin/physiology ; STAT3 Transcription Factor/physiology ; Interleukin-22
    Chemical Substances Interleukins ; Receptors, Interleukin ; STAT3 Transcription Factor ; Stat3 protein, mouse ; interleukin-22 receptor ; Imiquimod (P1QW714R7M)
    Language English
    Publishing date 2021-05-14
    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.2021.04.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: IL-17 and IL-22 are pivotal cytokines to delay wound healing of

    Lecron, Jean-Claude / Charreau, Sandrine / Jégou, Jean-François / Salhi, Nadjet / Petit-Paris, Isabelle / Guignouard, Emmanuel / Burucoa, Christophe / Favot-Laforge, Laure / Bodet, Charles / Barra, Anne / Huguier, Vincent / Mcheik, Jiad / Dumoutier, Laure / Garnier, Julien / Bernard, François-Xavier / Ryffel, Bernhard / Morel, Franck

    Frontiers in immunology

    2022  Volume 13, Page(s) 984016

    Abstract: Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory ...

    Abstract Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds.
    Methods: We have developed a mouse model of cutaneous wound healing, with or without wound inoculation with
    Results: Aseptic excision in C57BL/6 mouse skin induced early expression of IL-1β, TNFα and Oncostatin M (OSM), without detectable expression of IL-22 and IL-17A/F.
    Conclusion: These results demonstrate the synergistic and specific effects of IL-22 and IL-17 induced by bacterial infection delay the wound healing process, regardless of the presence of bacteria
    MeSH term(s) Mice ; Humans ; Animals ; Pseudomonas aeruginosa/metabolism ; Interleukin-17/metabolism ; Staphylococcus aureus/metabolism ; Tumor Necrosis Factor-alpha ; Oncostatin M ; Methicillin-Resistant Staphylococcus aureus/metabolism ; Mice, Inbred C57BL ; Interleukin-22
    Chemical Substances Interleukin-17 ; Tumor Necrosis Factor-alpha ; Oncostatin M (106956-32-5)
    Language English
    Publishing date 2022-10-07
    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.2022.984016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Development of SARS-CoV2 humoral response including neutralizing antibodies is not sufficient to protect patients against fatal infection.

    Choteau, Mathilde / Scohy, Anaïs / Messe, Stéphane / Luyckx, Mathieu / Dechamps, Mélanie / Montiel, Virginie / Yombi, Jean Cyr / Gruson, Damien / Limaye, Nisha / Michiels, Thomas / Dumoutier, Laure

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 2077

    Abstract: More than a year after the start of the pandemic, COVID-19 remains a global health emergency. Although the immune response against SARS-CoV-2 has been extensively studied, some points remain controversial. One is the role of antibodies in viral clearance ...

    Abstract More than a year after the start of the pandemic, COVID-19 remains a global health emergency. Although the immune response against SARS-CoV-2 has been extensively studied, some points remain controversial. One is the role of antibodies in viral clearance and modulation of disease severity. While passive transfer of neutralizing antibodies protects against SARS-CoV-2 infection in animal models, titers of anti-SARS-CoV-2 antibodies have been reported to be higher in patients suffering from more severe forms of the disease. A second key question for pandemic management and vaccine design is the persistence of the humoral response. Here, we characterized the antibody response in 187 COVID-19 patients, ranging from asymptomatic individuals to patients who died from COVID-19, and including patients who recovered. We developed in-house ELISAs to measure titers of IgG, IgM and IgA directed against the RBD or N regions in patient serum or plasma, and a spike-pseudotyped neutralization assay to analyse seroneutralization. Higher titers of virus-specific antibodies were detected in patients with severe COVID-19, including deceased patients, compared to asymptomatic patients. This demonstrates that fatal infection is not associated with defective humoral response. Finally, most of recovered patients still had anti-SARS-CoV-2 IgG more than 3 months after infection.
    MeSH term(s) Adult ; Aged ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/mortality ; Female ; Humans ; Immunity, Humoral ; Male ; Middle Aged ; SARS-CoV-2/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2022-02-08
    Publishing country England
    Document type Clinical Trial ; 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/s41598-022-06038-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Omalizumab in chronic spontaneous urticaria: A real-life experience of dose and intervals adjustments in Belgium.

    de Montjoye, Laurence / Herman, Anne / Dumoutier, Laure / Lambert, Michel / Tromme, Isabelle / Baeck, Marie

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2018  Volume 121, Issue 5, Page(s) 620–622

    MeSH term(s) Anti-Allergic Agents/administration & dosage ; Belgium ; Chronic Disease ; Dose-Response Relationship, Drug ; Humans ; Omalizumab/administration & dosage ; Treatment Outcome ; Urticaria/drug therapy
    Chemical Substances Anti-Allergic Agents ; Omalizumab (2P471X1Z11)
    Language English
    Publishing date 2018-07-06
    Publishing country United States
    Document type Letter
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2018.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Chilblains observed during the COVID-19 pandemic cannot be distinguished from classic, cold-related chilblains

    De Greef, Axel / Choteau, Mathilde / Herman, Anne / Bouzin, Caroline / Marot, Liliane / Dachelet, Claire / Lelotte, Julie / Hoton, Delphine / Dumoutier, Laure / Baeck, Marie

    European journal of dermatology : EJD

    2022  Volume 32, Issue 3, Page(s) 377–383

    Abstract: Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection.: Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to ... ...

    Title translation Chilblains observed during the COVID-19 pandemic cannot be distinguished from classic, cold-related chilblains.
    Abstract Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection.
    Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to focus on IFN-I expression in patients with chilblains.
    Materials & methods: A monocentric cohort of 43 patients presenting with CL from April 2020 to May 2021 were included. During this period, all CL were, a priori, considered to be SARS-CoV-2-related. RT-qPCR on nasopharyngeal swabs and measurements of anti-SARS-CoV-2 antibodies were performed. Anti-SARS-CoV-2 immunostainings as well as SARS-CoV-2 RT-qPCR were performed on biopsy specimens of CL and controls. Expression of MX1 and IRF7 was analysed on patients’ biopsy specimens and/or PBMC and compared with controls and/or chilblains observed before the pandemic. Serum IFN-α was also measured.
    Results: RT-qPCR was negative in all patients and serological tests were positive in 11 patients. Immunostaining targeting viral proteins confirmed the lack of specificity. SARS-CoV-2 RNA remained undetected in all CL specimens. MX1 immunostaining was positive in CL and in pre-pandemic chilblains compared to controls. MX1 and IRF7 expression was significantly increased in CL specimens but not in PBMC. Serum IFN-α was undetected in CL patients.
    Conclusion: CL observed during the pandemic do not appear to be directly related to SARS-CoV-2 infection, either based on viral cytopathogenicity or high IFN-I response induced by the virus.
    MeSH term(s) COVID-19/complications ; Chilblains/diagnosis ; Humans ; Interferon Regulatory Factor-7 ; Interferon-alpha ; Leukocytes, Mononuclear/immunology ; Myxovirus Resistance Proteins ; Pandemics ; RNA, Viral ; SARS-CoV-2
    Chemical Substances IRF7 protein, human ; Interferon Regulatory Factor-7 ; Interferon-alpha ; MX1 protein, human ; Myxovirus Resistance Proteins ; RNA, Viral
    Language English
    Publishing date 2022-09-05
    Publishing country France
    Document type Journal Article
    ZDB-ID 1128666-0
    ISSN 1952-4013 ; 1167-1122
    ISSN (online) 1952-4013
    ISSN 1167-1122
    DOI 10.1684/ejd.2022.4260
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer.

    de Heusch, Magali / Steenwinckel, Valérie / Cochez, Perrine M / Louahed, Jamila / Warnier, Guy / Lemaire, Muriel M / Renauld, Jean-Christophe / Dumoutier, Laure

    European journal of immunology

    2020  Volume 50, Issue 7, Page(s) 1034–1043

    Abstract: IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed ... ...

    Abstract IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4
    MeSH term(s) Adoptive Transfer/adverse effects ; Animals ; Colitis/etiology ; Colitis/genetics ; Colitis/immunology ; Colitis/pathology ; Disease Models, Animal ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/immunology ; Interleukin-2/genetics ; Interleukin-2/immunology ; Interleukin-9/genetics ; Interleukin-9/immunology ; Mice ; Mice, Knockout ; Mice, SCID ; Receptors, Interleukin-9/genetics ; Receptors, Interleukin-9/immunology ; Th17 Cells/immunology ; Th17 Cells/pathology ; Th17 Cells/transplantation ; Th2 Cells/immunology ; Th2 Cells/pathology ; Th2 Cells/transplantation
    Chemical Substances Cd44 protein, mouse ; Hyaluronan Receptors ; Il9r protein, mouse ; Interleukin-2 ; Interleukin-9 ; Receptors, Interleukin-9
    Language English
    Publishing date 2020-03-18
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201948430
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: IL-6 and IL-1β expression is increased in autologous serum skin test of patients with chronic spontaneous urticaria.

    de Montjoye, Laurence / Choteau, Mathilde / Herman, Anne / Hendrickx, Emilie / Chéou, Paméla / Baeck, Marie / Dumoutier, Laure

    Allergy

    2019  Volume 74, Issue 12, Page(s) 2522–2524

    MeSH term(s) Chronic Urticaria/diagnosis ; Chronic Urticaria/etiology ; Female ; Gene Expression ; Humans ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Leukocytes, Mononuclear/metabolism ; Male ; RNA, Messenger ; Skin Tests/methods
    Chemical Substances IL1B protein, human ; Interleukin-1beta ; Interleukin-6 ; RNA, Messenger
    Language English
    Publishing date 2019-06-20
    Publishing country Denmark
    Document type Letter
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.13928
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