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  1. Article ; Online: Lumpers and splitters: Birth of Th17 cells.

    Stockinger, Brigitta

    The Journal of experimental medicine

    2021  Volume 218, Issue 5

    Abstract: Th17 cells were born as a new subset of CD4 T cells to complement Th1, Th2, and T reg cells. From their identification as a distinct subset, they quickly became the paradigm for the astonishing plasticity that CD4 T cells can exhibit depending on tissue ... ...

    Abstract Th17 cells were born as a new subset of CD4 T cells to complement Th1, Th2, and T reg cells. From their identification as a distinct subset, they quickly became the paradigm for the astonishing plasticity that CD4 T cells can exhibit depending on tissue environment and circumstances.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/metabolism ; Humans ; Interleukin-17/metabolism ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/metabolism ; Th1 Cells/cytology ; Th1 Cells/metabolism ; Th17 Cells/cytology ; Th17 Cells/metabolism ; Th2 Cells/cytology ; Th2 Cells/metabolism
    Chemical Substances Interleukin-17
    Language English
    Publishing date 2021-04-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20210645
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  2. Article ; Online: T cell subsets and environmental factors in Citrobacter rodentium infection.

    Stockinger, Brigitta

    Current opinion in microbiology

    2021  Volume 63, Page(s) 92–97

    Abstract: Infection with Citrobacter rodentium constitutes an attack on the intestinal barrier and results in concerted action by innate and adaptive immune responses to limit bacterial translocation and destroy those bacteria that have breached the intestinal ... ...

    Abstract Infection with Citrobacter rodentium constitutes an attack on the intestinal barrier and results in concerted action by innate and adaptive immune responses to limit bacterial translocation and destroy those bacteria that have breached the intestinal barrier. Among the many immune cell types that are involved in the defence against this infection, Th17 cells as the major producers of the barrier protective cytokine IL-22 during the adaptive phase of the response are most numerous. Their extensive plasticity furthermore results in the production of additional cytokines that previously were ascribed to Th1 cells, such as IFNγ. The timely and coordinated repair of damaged epithelium requires input from environmental factors derived from diet and microbiota metabolism of tryptophan which are transmitted through the aryl hydrocarbon receptor (AHR). Thus, the combination of a robust immune response, coupled with intestinal stem cell differentiation guided by environmental factors, ensures resistance to barrier destruction by intestinal infection.
    MeSH term(s) Animals ; Citrobacter rodentium ; Enterobacteriaceae Infections ; Intestinal Mucosa ; Mice ; Mice, Inbred C57BL ; T-Lymphocyte Subsets ; Th17 Cells
    Language English
    Publishing date 2021-07-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2021.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: T cell subsets and environmental factors in Citrobacter rodentium infection

    Stockinger, Brigitta

    Current opinion in microbiology. 2021 Oct., v. 63

    2021  

    Abstract: Infection with Citrobacter rodentium constitutes an attack on the intestinal barrier and results in concerted action by innate and adaptive immune responses to limit bacterial translocation and destroy those bacteria that have breached the intestinal ... ...

    Abstract Infection with Citrobacter rodentium constitutes an attack on the intestinal barrier and results in concerted action by innate and adaptive immune responses to limit bacterial translocation and destroy those bacteria that have breached the intestinal barrier. Among the many immune cell types that are involved in the defence against this infection, Th17 cells as the major producers of the barrier protective cytokine IL-22 during the adaptive phase of the response are most numerous. Their extensive plasticity furthermore results in the production of additional cytokines that previously were ascribed to Th1 cells, such as IFNγ. The timely and coordinated repair of damaged epithelium requires input from environmental factors derived from diet and microbiota metabolism of tryptophan which are transmitted through the aryl hydrocarbon receptor (AHR). Thus, the combination of a robust immune response, coupled with intestinal stem cell differentiation guided by environmental factors, ensures resistance to barrier destruction by intestinal infection.
    Keywords Citrobacter rodentium ; T-lymphocytes ; aryl hydrocarbon receptors ; cell differentiation ; cytokines ; diet ; epithelium ; gastrointestinal diseases ; immune response ; intestines ; metabolism ; plasticity ; stem cells ; tryptophan
    Language English
    Dates of publication 2021-10
    Size p. 92-97.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2021.06.006
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  4. Article ; Online: Open questions: a few that need answers in immunology.

    Stockinger, Brigitta

    BMC biology

    2013  Volume 11, Page(s) 115

    MeSH term(s) Humans ; Immunity, Innate ; Interleukin-17/immunology ; Lymphocytes/immunology ; Receptors, Cytoplasmic and Nuclear/immunology ; Th17 Cells/immunology
    Chemical Substances Interleukin-17 ; Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2013-11-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2133020-7
    ISSN 1741-7007 ; 1741-7007
    ISSN (online) 1741-7007
    ISSN 1741-7007
    DOI 10.1186/1741-7007-11-115
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  5. Article ; Online: Dysregulation of the Environmental Sensor Aryl Hydrocarbon Receptor Affects Differentiation of Human Colon Organoids.

    Liebert, Anke / Shapiro, Michael / Maradana, Muralidhara Rao / Li, Ying / Powell, Nick / Zilbauer, Matthias / Stockinger, Brigitta

    Cellular and molecular gastroenterology and hepatology

    2023  Volume 17, Issue 3, Page(s) 507–510

    MeSH term(s) Humans ; Receptors, Aryl Hydrocarbon/genetics ; Colon
    Chemical Substances Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2819778-1
    ISSN 2352-345X ; 2352-345X
    ISSN (online) 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2023.11.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: AHR in the intestinal microenvironment: safeguarding barrier function.

    Stockinger, Brigitta / Shah, Kathleen / Wincent, Emma

    Nature reviews. Gastroenterology & hepatology

    2021  Volume 18, Issue 8, Page(s) 559–570

    Abstract: Mammalian aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that belongs to the basic helix-loop-helix (bHLH)-PAS family of transcription factors, which are evolutionarily conserved environmental sensors. In the absence of ... ...

    Abstract Mammalian aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that belongs to the basic helix-loop-helix (bHLH)-PAS family of transcription factors, which are evolutionarily conserved environmental sensors. In the absence of ligands, AHR resides in the cytoplasm in a complex with molecular chaperones such as HSP90, XAP2 and p23. Upon ligand binding, AHR translocates into the nuclear compartment, where it dimerizes with its partner protein, AHR nuclear translocator (ARNT), an obligatory partner for the DNA-binding and functional activity. Historically, AHR had mostly been considered as a key intermediary for the detrimental effects of environmental pollutants on the body. However, following the discovery of AHR-mediated functions in various immune cells, as well as the emergence of non-toxic 'natural' AHR ligands, this view slowly began to change, and the study of AHR-deficient mice revealed a plethora of important beneficial functions linked to AHR activation. This Review focuses on regulation of the AHR pathway and the barrier-protective roles AHR has in haematopoietic, as well as non-haematopoietic, cells within the intestinal microenvironment. It covers the nature of AHR ligands and feedback regulation of the AHR pathway, outlining the currently known physiological functions in immune, epithelial, endothelial and neuronal cells of the intestine.
    MeSH term(s) Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator/physiology ; Feedback, Physiological ; Humans ; Intestinal Mucosa/metabolism ; Mice ; Receptors, Aryl Hydrocarbon/physiology ; Transcription Factors/physiology ; Transcriptional Activation/physiology
    Chemical Substances Receptors, Aryl Hydrocarbon ; Transcription Factors ; Aryl Hydrocarbon Receptor Nuclear Translocator (138391-32-9)
    Language English
    Publishing date 2021-03-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2493722-8
    ISSN 1759-5053 ; 1759-5045
    ISSN (online) 1759-5053
    ISSN 1759-5045
    DOI 10.1038/s41575-021-00430-8
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  7. Article ; Online: The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice.

    Diny, Nicola Laura / Schonfeldova, Barbora / Shapiro, Michael / Winder, Matthew L / Varsani-Brown, Sunita / Stockinger, Brigitta

    The Journal of experimental medicine

    2022  Volume 219, Issue 4

    Abstract: Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and ... ...

    Abstract Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response, cell-cell communication, extracellular matrix remodeling, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis. Eosinophils from AHR-deficient mice failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. AHR-deficient eosinophils were functionally impaired in the adhesion to and degradation of extracellular matrix, were more prone to degranulation, and had an extended life span. Lack of AHR in eosinophils had wider effects on the intestinal immune system, affecting the T cell compartment in nave and helminth-infected mice. Our study demonstrates that the response to environmental triggers via AHR partially shapes tissue adaptation of eosinophils in the small intestine.
    MeSH term(s) Animals ; Eosinophils/metabolism ; Homeostasis ; Intestine, Small ; Mice ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/metabolism
    Chemical Substances Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2022-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20210970
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  8. Article ; Online: PairGP: Gaussian process modeling of longitudinal data from paired multi-condition studies.

    Vantini, Michele / Mannerström, Henrik / Rautio, Sini / Ahlfors, Helena / Stockinger, Brigitta / Lähdesmäki, Harri

    Computers in biology and medicine

    2022  Volume 143, Page(s) 105268

    Abstract: High-throughput technologies produce gene expression time-series data that need fast and specialized algorithms to be processed. While current methods already deal with different aspects, such as the non-stationarity of the process and the temporal ... ...

    Abstract High-throughput technologies produce gene expression time-series data that need fast and specialized algorithms to be processed. While current methods already deal with different aspects, such as the non-stationarity of the process and the temporal correlation, they often fail to take into account the pairing among replicates. We propose PairGP, a non-stationary Gaussian process method to compare gene expression time-series across several conditions that can account for paired longitudinal study designs and can identify groups of conditions that have different gene expression dynamics. We demonstrate the method on both simulated data and previously unpublished RNA sequencing (RNA-seq) time-series with five conditions. The results show the advantage of modeling the pairing effect to better identify groups of conditions with different dynamics. The pairing effect model displays good capabilities of selecting the most probable grouping of conditions even in the presence of a high number of conditions. The developed method is of general application and can be applied to any gene expression time series dataset. The model can identify common replicate effects among the samples coming from the same biological replicates and model those as separate components. Learning the pairing effect as a separate component, not only allows us to exclude it from the model to get better estimates of the condition effects, but also to improve the precision of the model selection process. The pairing effect that was accounted before as noise, is now identified as a separate component, resulting in more accurate and explanatory models of the data.
    Language English
    Publishing date 2022-01-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 127557-4
    ISSN 1879-0534 ; 0010-4825
    ISSN (online) 1879-0534
    ISSN 0010-4825
    DOI 10.1016/j.compbiomed.2022.105268
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  9. Article ; Online: The dichotomous nature of T helper 17 cells.

    Stockinger, Brigitta / Omenetti, Sara

    Nature reviews. Immunology

    2017  Volume 17, Issue 9, Page(s) 535–544

    Abstract: T helper 17 ( ... ...

    Abstract T helper 17 (T
    MeSH term(s) Cell Plasticity/immunology ; Gastrointestinal Microbiome/immunology ; Gene Expression Profiling ; Humans ; Immunity, Mucosal/immunology ; Inflammation/immunology ; Inflammatory Bowel Diseases/immunology ; Intestinal Mucosa/metabolism ; Intestines/immunology ; Intestines/microbiology ; Permeability ; Th17 Cells/immunology ; Th17 Cells/metabolism
    Language English
    Publishing date 2017-05-30
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/nri.2017.50
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  10. Article ; Online: Manuka honey activates the aryl hydrocarbon receptor: Implications for skin inflammation.

    Alangari, Abdullah A / Ashoori, Matin D / Alwan, Wisam / Dawe, Hannah R / Stockinger, Brigitta / Barker, Jonathan N / Wincent, Emma / Di Meglio, Paola

    Pharmacological research

    2023  Volume 194, Page(s) 106848

    Abstract: Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH down regulates IL-4-induced CCL26 expression in immortalized keratinocytes. As MH contains potential ... ...

    Abstract Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH down regulates IL-4-induced CCL26 expression in immortalized keratinocytes. As MH contains potential ligands of the Aryl Hydrocarbon Receptor (AHR), a key regulator of skin homeostasis, we hypothesize that this effect is mediated via AHR activation. Here, we treated HaCaT cell lines, either stable transfected with an empty vector (EV-HaCaT) or in which AHR had been stable silenced (AHR-silenced HaCaT); or primary normal human epithelial keratinocytes (NHEK) with 2% MH for 24 h. This induced a 15.4-fold upregulation of CYP1A1 in EV-HaCaTs, which was significantly reduced in AHR-silenced cells. Pre-treatment with the AHR antagonist CH223191 completely abrogated this effect. Similar findings were observed in NHEK. In vivo treatment of the Cyp1a1
    MeSH term(s) Animals ; Humans ; Mice ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; Dermatitis ; Honey ; Inflammation ; Interleukin-4/immunology ; Receptors, Aryl Hydrocarbon/metabolism
    Chemical Substances 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Interleukin-4 (207137-56-2) ; Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2023-07-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2023.106848
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