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  1. Article ; Online: Analysis of the interplay between hepatitis B virus-positive hepatocytes and Kupffer cells ex vivo using mice as a model

    Yumei Li / Jiyoung Lee / Doumet Georges Helou / Omid Akbari / Jing-hsiung James Ou

    STAR Protocols, Vol 3, Iss 2, Pp 101364- (2022)

    2022  

    Abstract: Summary: Kupffer cells play critical roles in both hepatitis B virus (HBV) persistence and clearance. Here, we provide a protocol for studying the interplay between Kupffer cells and HBV-positive hepatocytes ex vivo using mice as a model. This protocol ... ...

    Abstract Summary: Kupffer cells play critical roles in both hepatitis B virus (HBV) persistence and clearance. Here, we provide a protocol for studying the interplay between Kupffer cells and HBV-positive hepatocytes ex vivo using mice as a model. This protocol includes hydrodynamic injection of HBV DNA into mouse hepatocytes, liver perfusion for isolating hepatocytes and Kupffer cells, and Seahorse metabolic analysis of Kupffer cells. This protocol allows the detailed analysis of how HBV-positive hepatocytes and Kupffer cells impact each other ex vivo.For complete details on the use and execution of this protocol, please refer to Li et al. (2022).
    Keywords Cell Biology ; Cell culture ; Cell isolation ; Immunology ; Metabolism ; Microbiology ; Science (General) ; Q1-390
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability

    Benjamin P. Hurrell / Doumet Georges Helou / Emily Howard / Jacob D. Painter / Pedram Shafiei-Jahani / Arlene H. Sharpe / Omid Akbari

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: Regulatory T (Treg) cells have been implicated in the induction of airway tolerance and amelioration of respiratory duct inflammation. Here the authors show, using PD-L2 deficient mice, that the immune suppression signal from PD-L2 is important for ... ...

    Abstract Regulatory T (Treg) cells have been implicated in the induction of airway tolerance and amelioration of respiratory duct inflammation. Here the authors show, using PD-L2 deficient mice, that the immune suppression signal from PD-L2 is important for modulating Treg cell metabolism and function for proper induction of respiratory tolerance in mice.
    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.

    Doumet Georges Helou / Aurélie Mauras / François Fasquelle / Juliane Sousa Lanza / Philippe M Loiseau / Didier Betbeder / Sandrine Cojean

    PLoS Neglected Tropical Diseases, Vol 15, Iss 8, p e

    2021  Volume 0009627

    Abstract: Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an ...

    Abstract Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 630
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: TNFR2 Signaling Enhances ILC2 Survival, Function, and Induction of Airway Hyperreactivity

    Benjamin P. Hurrell / Lauriane Galle-Treger / Pedram Shafiei Jahani / Emily Howard / Doumet Georges Helou / Homayon Banie / Pejman Soroosh / Omid Akbari

    Cell Reports, Vol 29, Iss 13, Pp 4509-4524.e

    2019  Volume 5

    Abstract: Summary: Group 2 innate lymphoid cells (ILC2s) can initiate pathologic inflammation in allergic asthma by secreting copious amounts of type 2 cytokines, promoting lung eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. We ... ...

    Abstract Summary: Group 2 innate lymphoid cells (ILC2s) can initiate pathologic inflammation in allergic asthma by secreting copious amounts of type 2 cytokines, promoting lung eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. We discovered that the TNF/TNFR2 axis is a central immune checkpoint in murine and human ILC2s. ILC2s selectively express TNFR2, and blocking the TNF/TNFR2 axis inhibits survival and cytokine production and reduces ILC2-dependent AHR. The mechanism of action of TNFR2 in ILC2s is through the non-canonical NF-κB pathway as an NF-κB-inducing kinase (NIK) inhibitor blocks the costimulatory effect of TNF-α. Similarly, human ILC2s selectively express TNFR2, and using hILC2s, we show that TNFR2 engagement promotes AHR through a NIK-dependent pathway in alymphoid murine recipients. These findings highlight the role of the TNF/TNFR2 axis in pulmonary ILC2s, suggesting that targeting TNFR2 or relevant signaling is a different strategy for treating patients with ILC2-dependent asthma. : TNF-α is highly expressed in the lungs of asthmatic patients. Hurrell et al. show that murine and human ILC2s respond to TNF-α by selectively expressing TNFR2. TNF-α enhances ILC2 survival and cytokine production utilizing the non-canonical NF-κB pathway, leading to increased development of ILC2-dependent AHR. Keywords: ILC2, TNF-a, TNFR2, airway hyperreactivity, NIK, NIK inhibitor, asthma, activation
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Autophagy impairment in liver CD11c+ cells promotes non-alcoholic fatty liver disease through production of IL-23

    Lauriane Galle-Treger / Doumet Georges Helou / Christine Quach / Emily Howard / Benjamin P. Hurrell / German R. Aleman Muench / Pedram Shafiei-Jahani / Jacob D. Painter / Andrea Iorga / Lily Dara / Juliet Emamaullee / Lucy Golden-Mason / Hugo R. Rosen / Pejman Soroosh / Omid Akbari

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: The function of autophagy and how this affects non-alcoholic fatty liver disease is not fully known. Here the authors show that in mice with a targeted disruption of the autophagy pathway in CD11c+ cells, development of NAFLD is accelerated involving IL- ... ...

    Abstract The function of autophagy and how this affects non-alcoholic fatty liver disease is not fully known. Here the authors show that in mice with a targeted disruption of the autophagy pathway in CD11c+ cells, development of NAFLD is accelerated involving IL-23 and blocking of IL-23 reduces disease.
    Keywords Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

    Pedram Shafiei-Jahani / Doumet Georges Helou / Benjamin P. Hurrell / Emily Howard / Christine Quach / Jacob D. Painter / Lauriane Galle-Treger / Meng Li / Yong-Hwee Eddie Loh / Omid Akbari

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: The role of the CD200–CD200R axis in regulating pulmonary inflammation is not completely understood. Here the authors show CD200R is expressed on type 2 innate lymphoid cells (ILC2s), and its engagement by CD200 ameliorates airway hyperreactivity and ... ...

    Abstract The role of the CD200–CD200R axis in regulating pulmonary inflammation is not completely understood. Here the authors show CD200R is expressed on type 2 innate lymphoid cells (ILC2s), and its engagement by CD200 ameliorates airway hyperreactivity and allergic asthma via inhibition of NF-κB signaling.
    Keywords Science ; Q
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

    Doumet Georges Helou / Pedram Shafiei-Jahani / Richard Lo / Emily Howard / Benjamin P. Hurrell / Lauriane Galle-Treger / Jacob D. Painter / Gavin Lewis / Pejman Soroosh / Arlene H. Sharpe / Omid Akbari

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice ...

    Abstract PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice and provide evidence that PD-1 signaling alters ILC2 function by modulation of cell metabolism.
    Keywords Science ; Q
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

    Doumet Georges Helou / Pedram Shafiei-Jahani / Richard Lo / Emily Howard / Benjamin P. Hurrell / Lauriane Galle-Treger / Jacob D. Painter / Gavin Lewis / Pejman Soroosh / Arlene H. Sharpe / Omid Akbari

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice ...

    Abstract PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice and provide evidence that PD-1 signaling alters ILC2 function by modulation of cell metabolism.
    Keywords Science ; Q
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

    Pedram Shafiei-Jahani / Benjamin P. Hurrell / Lauriane Galle-Treger / Doumet Georges Helou / Emily Howard / Jacob Painter / Richard Lo / Gavin Lewis / Pejman Soroosh / Omid Akbari

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin- ... ...

    Abstract Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration.

    Doumet Georges Helou / Sarah Braham / Luc De Chaisemartin / Vanessa Granger / Marie-Hélène Damien / Marc Pallardy / Saadia Kerdine-Römer / Sylvie Chollet-Martin

    PLoS ONE, Vol 14, Iss 8, p e

    2019  Volume 0216465

    Abstract: Polymorphonuclear neutrophils (PMNs) are the first line of defense against pathogens and their activation needs to be tightly regulated in order to limit deleterious effects. Nrf2 (Nuclear factor (erythroïd-derived 2)-like 2) transcription factor ... ...

    Abstract Polymorphonuclear neutrophils (PMNs) are the first line of defense against pathogens and their activation needs to be tightly regulated in order to limit deleterious effects. Nrf2 (Nuclear factor (erythroïd-derived 2)-like 2) transcription factor regulates oxidative stress and/or represses inflammation in various cells such as dendritic cells or macrophages. However, its involvement in PMN biology is still unclear. Using Nrf2 KO mice, we thus aimed to investigate the protective role of Nrf2 in various PMN functions such as oxidative burst, netosis, migration, cytokine production and phagocytosis, mainly in response to zymosan. We found that zymosan induced Nrf2 accumulation in PMNs leading to the upregulation of some target genes including Hmox-1, Nqo1 and Cat. Nrf2 was able to decrease zymosan-induced PMN oxidative burst; sulforaphane-induced Nrf2 hyperexpression confirmed its implication. Tnfα, Ccl3 and Cxcl2 gene transcription was decreased in zymosan-stimulated Nrf2 KO PMNs, suggesting a role for Nrf2 in the regulation of proinflammatory cytokine production. However, Nrf2 was not involved in phagocytosis. Finally, spontaneous migration of Nrf2 KO PMNs was lower than that of WT PMNs. Moreover, in response to low concentrations of CXCL2 or CXCL12, Nrf2 KO PMN migration was decreased despite similar CXCR2 and CXCR4 expression and ATP levels in PMNs from both genotypes. Nrf2 thus seems to be required for an optimal migration. Altogether these results suggest that Nrf2 has a protective role in several PMN functions. In particular, it downregulates their activation in response to zymosan and is required for an adequate migration.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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