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  1. Article ; Online: Thymic stromal lymphopoietin, skin barrier dysfunction, and the atopic march.

    Ziegler, Steven F

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

    2021  Volume 127, Issue 3, Page(s) 306–311

    Abstract: Objective: Atopic dermatitis often precedes the development of other atopic diseases, and the atopic march describes this temporal relationship in the natural history of these diseases. Although the pathophysiological mechanisms that underlie this ... ...

    Abstract Objective: Atopic dermatitis often precedes the development of other atopic diseases, and the atopic march describes this temporal relationship in the natural history of these diseases. Although the pathophysiological mechanisms that underlie this relationship are poorly understood, epidemiologic and genetic data have suggested that the skin might be an important route of sensitization to allergens.
    Data sources: Review of recent studies on the role of skin barrier defects in systemic allergen sensitization.
    Study selections: Recent publications on the relationship between skin barrier defects and expression of epithelial cell-derived cytokines.
    Results: Animal models have begun to elucidate on how skin barrier defects can lead to systemic allergen sensitization. Emerging data now suggest that epithelial cell-derived cytokines, such as thymic stromal lymphopoietin, drive the progression from atopic dermatitis to asthma and food allergy. Skin barrier defects can lead to induction of epithelial cell-derived cytokines, which in turn leads to the initiation and maintenance of allergic inflammation and the atopic march.
    Conclusion: Development of new biologic drug targeting type 2 cytokines provides novel therapeutic interventions for atopic dermatitis.
    MeSH term(s) Animals ; Cytokines/immunology ; Humans ; Hypersensitivity, Immediate/complications ; Hypersensitivity, Immediate/genetics ; Hypersensitivity, Immediate/immunology ; Skin/immunology ; Thymic Stromal Lymphopoietin
    Chemical Substances Cytokines ; Thymic Stromal Lymphopoietin (GT0IL38SP4)
    Language English
    Publishing date 2021-06-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    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.2021.06.004
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  2. Article ; Online: B cell- and T cell-intrinsic regulation of germinal centers by thymic stromal lymphopoietin signaling.

    Domeier, Phillip P / Rahman, Ziaur S M / Ziegler, Steven F

    Science immunology

    2023  Volume 8, Issue 79, Page(s) eadd9413

    Abstract: Long-lived and high-affinity antibodies are derived from germinal center (GC) activity, but the cytokines that regulate GC function are still being identified. Here, we show that thymic stromal lymphopoietin (TSLP) signaling regulates the GC and the ... ...

    Abstract Long-lived and high-affinity antibodies are derived from germinal center (GC) activity, but the cytokines that regulate GC function are still being identified. Here, we show that thymic stromal lymphopoietin (TSLP) signaling regulates the GC and the magnitude of antigen-specific antibody responses. Both GC B cells and T follicular helper (T
    MeSH term(s) Cytokines ; Germinal Center/metabolism ; Receptors, Cytokine/metabolism ; Signal Transduction ; T-Lymphocytes/metabolism ; Thymic Stromal Lymphopoietin ; B-Lymphocytes/metabolism
    Chemical Substances Cytokines ; Receptors, Cytokine ; Thymic Stromal Lymphopoietin (GT0IL38SP4)
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.add9413
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  3. Article ; Online: Investigating Thymic Epithelial Cell Diversity Using Systems Biology.

    Chiu, Honyin / Linsley, Peter S / Ziegler, Steven F

    Journal of immunology (Baltimore, Md. : 1950)

    2023  Volume 210, Issue 7, Page(s) 888–894

    Abstract: The thymus is an intricate organ consisting of a diverse population of thymic epithelial cells (TECs). Cortical and medullary TECs and their subpopulations have distinct roles in coordinating the development and selection of functionally competent and ... ...

    Abstract The thymus is an intricate organ consisting of a diverse population of thymic epithelial cells (TECs). Cortical and medullary TECs and their subpopulations have distinct roles in coordinating the development and selection of functionally competent and self-tolerant T cells. Recent advances made in technologies such as single-cell RNA sequencing have made it possible to investigate and resolve the heterogeneity in TECs. These findings have provided further understanding of the molecular mechanisms regulating TEC function and expression of tissue-restricted Ags. In this brief review, we focus on the newly characterized subsets of TECs and their diversity in relation to their functions in supporting T cell development. We also discuss recent discoveries in expression of self-antigens in the context of TEC development as well as the cellular and molecular changes occurring during embryonic development to thymic involution.
    MeSH term(s) Systems Biology ; T-Lymphocytes ; Thymus Gland ; Epithelial Cells ; Cell Differentiation
    Language English
    Publishing date 2023-03-22
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2200610
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  4. Article: Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection.

    Norris, Geoffrey T / Ames, Joshua M / Ziegler, Steven F / Oberst, Andrew

    bioRxiv : the preprint server for biology

    2023  

    Abstract: In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, ... ...

    Abstract In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, essential function, and limited capacity for self-renewal render it susceptible to both pathogen- and immune-mediated pathology. Here, we identify the alarmin IL-33 and its receptor ST2 as critical for host survival to neuroinvasive flavivirus infection. We identify oligodendrocytes as the critical source of IL-33, and microglia as the key cellular responders. Notably, we find that the IL-33/ST2 axis does not impact viral control or adaptive immune responses; rather, it is required to promote the activation and survival of microglia. In the absence of intact IL-33/ST2 signaling in the brain, neuroinvasive flavivirus infection triggered aberrant recruitment of monocyte-derived peripheral immune cells, increased neuronal stress, and neuronal cell death, effects that compromised organismal survival. These findings identify IL-33 as a critical mediator of CNS tolerance to pathogen-initiated immunity and inflammation.
    Language English
    Publishing date 2023-04-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.11.536332
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  5. Article ; Online: Division of labour by CD4(+) T helper cells.

    Ziegler, Steven F

    Nature reviews. Immunology

    2016  Volume 16, Issue 7, Page(s) 403

    Language English
    Publishing date 2016-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/nri.2016.53
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  6. Article ; Online: Emerging role for thymic stromal lymphopoietin-responsive regulatory T cells in colorectal cancer progression in humans and mice.

    Obata-Ninomiya, Kazushige / de Jesus Carrion, Steven / Hu, Alex / Ziegler, Steven F

    Science translational medicine

    2022  Volume 14, Issue 645, Page(s) eabl6960

    Abstract: Recruitment of regulatory T cells ( ... ...

    Abstract Recruitment of regulatory T cells (T
    MeSH term(s) Animals ; Colorectal Neoplasms/metabolism ; Cytokines/metabolism ; Humans ; Mice ; Receptors, Cytokine/metabolism ; T-Lymphocytes, Regulatory
    Chemical Substances Cytokines ; Receptors, Cytokine ; thymic stromal lymphopoietin (GT0IL38SP4)
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abl6960
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  7. Article ; Online: Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection.

    Norris, Geoffrey T / Ames, Joshua M / Ziegler, Steven F / Oberst, Andrew

    PLoS pathogens

    2023  Volume 19, Issue 11, Page(s) e1011350

    Abstract: In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, ... ...

    Abstract In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, essential function, and limited capacity for self-renewal render it susceptible to both pathogen- and immune-mediated pathology. Here, we identify the alarmin IL-33 and its receptor ST2 as critical for host survival to neuroinvasive flavivirus infection. We identify oligodendrocytes as the critical source of IL-33, and microglia as the key cellular responders. Notably, we find that the IL-33/ST2 axis does not impact viral control or adaptive immune responses; rather, it is required to promote the activation and survival of microglia. In the absence of intact IL-33/ST2 signaling in the brain, neuroinvasive flavivirus infection triggered aberrant recruitment of monocyte-derived peripheral immune cells, increased neuronal stress, and neuronal cell death, effects that compromised organismal survival. These findings identify IL-33 as a critical mediator of CNS tolerance to pathogen-initiated immunity and inflammation.
    MeSH term(s) Humans ; Central Nervous System ; Flavivirus Infections/metabolism ; Interleukin-1 Receptor-Like 1 Protein/metabolism ; Interleukin-33/metabolism ; Microglia/metabolism ; Animals ; Mice
    Chemical Substances Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33 ; Il33 protein, mouse
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011350
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  8. Article ; Online: Profiling of Tregs across tissues reveals plasticity in ST2 expression and hierarchies in tissue-specific phenotypes.

    Spath, Sabine / Roan, Florence / Presnell, Scott R / Höllbacher, Barbara / Ziegler, Steven F

    iScience

    2022  Volume 25, Issue 9, Page(s) 104998

    Abstract: ... ...

    Abstract Foxp3
    Language English
    Publishing date 2022-08-24
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104998
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  9. Article ; Online: Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

    Malinczak, Carrie-Anne / Fonseca, Wendy / Hrycaj, Steven M / Morris, Susan B / Rasky, Andrew J / Yagi, Kazuma / Wellik, Deneen M / Ziegler, Steven F / Zemans, Rachel L / Lukacs, Nicholas W

    American journal of physiology. Lung cellular and molecular physiology

    2024  Volume 326, Issue 3, Page(s) L280–L291

    Abstract: Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested ... ...

    Abstract Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in
    MeSH term(s) Humans ; Infant ; Animals ; Mice ; Respiratory Syncytial Virus Infections ; Lung/pathology ; Pneumonia/complications ; Lung Diseases/complications ; Respiratory Syncytial Virus, Human ; Mice, Inbred BALB C
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00300.2023
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  10. Article ; Online: TSLP: from allergy to cancer.

    Corren, Jonathan / Ziegler, Steven F

    Nature immunology

    2019  Volume 20, Issue 12, Page(s) 1603–1609

    Abstract: The cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers. While the role of TSLP in type 2 immune responses has been investigated extensively, recent studies have ... ...

    Abstract The cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers. While the role of TSLP in type 2 immune responses has been investigated extensively, recent studies have found an expanding role for TSLP in inflammatory diseases and cancer. In this Review, we will highlight major recent advances in TSLP biology, along with results from emerging clinical trials of anti-TSLP agents used for the treatment of a variety of inflammatory conditions.
    MeSH term(s) Animals ; Clinical Trials as Topic ; Cytokines/metabolism ; Homeostasis ; Humans ; Hypersensitivity/metabolism ; Inflammation/immunology ; Interleukin-7/metabolism ; Lymphopoiesis ; Neoplasms/metabolism ; Protein Isoforms/metabolism ; Receptors, Cytokine/metabolism
    Chemical Substances CRLF2 protein, human ; Cytokines ; Interleukin-7 ; Protein Isoforms ; Receptors, Cytokine ; thymic stromal lymphopoietin (GT0IL38SP4)
    Language English
    Publishing date 2019-11-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-019-0524-9
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