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  1. Article ; Online: Role of Autophagy in Lung Inflammation

    Jacob D. Painter / Lauriane Galle-Treger / Omid Akbari

    Frontiers in Immunology, Vol

    2020  Volume 11

    Abstract: Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents ... ...

    Abstract Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a TH17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between TH2 and TH17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.
    Keywords autophagy ; asthma ; lung inflammation ; immunometabolism ; COVID-19 ; SARS-CoV-2 ; Immunologic diseases. Allergy ; RC581-607 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. 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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  3. 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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  4. 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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  5. 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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  6. Article ; Online: Feasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity.

    Fred R Sattler / Melissa Mert / Ishwarya Sankaranarayanan / Wendy J Mack / Lauriane Galle-Treger / Evelyn Gonzalez / Lilit Baronikian / Kyuwan Lee / Pedram Shafiei Jahani / Howard N Hodis / Christina Dieli-Conwright / Omid Akbari

    PLoS ONE, Vol 15, Iss 9, p e

    2020  Volume 0237496

    Abstract: Background Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and ... ...

    Abstract Background Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and innate mononuclear white cells in obese non-diabetic adults in response to a dipeptidyl protease inhibitor (DPP4i), known to inhibit activation of immune white cells. Methods Adults 18-55 years-of-age were screened for abdominal obesity and insulin resistance or impaired glucose tolerance but without known inflammatory conditions. Twenty-one eligible participants consented for study and were randomized 3:1 to receive sitagliptin (DPP4i) at 100mg or matching placebo daily for 28 days. Abdominal AT collected by percutaneous biopsy and peripheral blood mononuclear cell fractions were evaluated before and after treatment; plasma was stored for batch testing. Results Highly sensitive C-reactive protein, a global marker of inflammation, was not elevated in the study population. Innate lymphoid cells (ILC) type 3 (ILC-3) in abdominal AT decreased with active treatment compared with placebo (p = 0.04). Other immune white cells in AT and peripheral blood mononuclear cell (PBMC) fractions did not change with treatment compared to placebo (p>0.05); although ILC-2 declined in PBMCs (p = 0.007) in the sitagliptin treatment group. Two circulating biomarkers of atherogenesis, interferon-inducible protein-10 (IP-10) and sCD40L declined in plasma (p = 0.02 and p = 0.07, respectively) in the active treatment group, providing indirect validation of a net reduction in inflammation. Conclusions In this pilot study, two cell types of the innate lymphoid system, ILC-3 in AT and ILC-2 PBMCs declined during treatment and as did circulating biomarkers of atherogenesis. Changes in other immune cells were not demonstrable. The study showed that sufficient abdominal AT could be obtained to quantify white cells of both innate and adaptive immunity and to demonstrate changes during therapy ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  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 Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. 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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  9. Article ; Online: Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

    Lauriane Galle-Treger / Yuzo Suzuki / Nisheel Patel / Ishwarya Sankaranarayanan / Jennifer L. Aron / Hadi Maazi / Lin Chen / Omid Akbari

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 13

    Abstract: Airway hyperreactivity is driven by type 2 cytokines produced by ILC2 and Th2 cells. Here the authors show that an α7-nicotinic receptor agonist (GTS-21) inhibits ILC2 responses and is therapeutic against Alternaria-induced airway hyperreactivity in a ... ...

    Abstract Airway hyperreactivity is driven by type 2 cytokines produced by ILC2 and Th2 cells. Here the authors show that an α7-nicotinic receptor agonist (GTS-21) inhibits ILC2 responses and is therapeutic against Alternaria-induced airway hyperreactivity in a humanized mouse model.
    Keywords Science ; Q
    Language English
    Publishing date 2016-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes

    Lauriane Galle-Treger / Ishwarya Sankaranarayanan / Benjamin P. Hurrell / Emily Howard / Richard Lo / Hadi Maazi / Gavin Lewis / Homayon Banie / Alan L. Epstein / Peisheng Hu / Virender K. Rehan / Frank D. Gilliland / Hooman Allayee / Pejman Soroosh / Arlene H. Sharpe / Omid Akbari

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: Type-2 innate lymphoid cells (ILC2s) are an immune population secreting Th2 cytokines playing a role in the regulation of adipose metabolic homeostasis. Here the authors show that engagement of GITR, a member of the TNF superfamily, in activated ILC2s is ...

    Abstract Type-2 innate lymphoid cells (ILC2s) are an immune population secreting Th2 cytokines playing a role in the regulation of adipose metabolic homeostasis. Here the authors show that engagement of GITR, a member of the TNF superfamily, in activated ILC2s is protective against insulin resistance in both a preventive and a therapeutic manner in the context of obesity.
    Keywords Science ; Q
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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