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  1. Article ; Online: Mucosal immune responses in COVID19 - a living review.

    Pearson, Claire F / Jeffery, Rebecca / Thornton, Emily E

    Oxford open immunology

    2021  Volume 2, Issue 1, Page(s) iqab002

    Abstract: COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a ... ...

    Abstract COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Journal Article
    ISSN 2633-6960
    ISSN (online) 2633-6960
    DOI 10.1093/oxfimm/iqab002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immune microniches shape intestinal T

    Gu, Yisu / Bartolomé-Casado, Raquel / Xu, Chuan / Bertocchi, Alice / Janney, Alina / Heuberger, Cornelia / Pearson, Claire F / Teichmann, Sarah A / Thornton, Emily E / Powrie, Fiona

    Nature

    2024  Volume 628, Issue 8009, Page(s) 854–862

    Abstract: The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading ... ...

    Abstract The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading pathogens
    MeSH term(s) Animals ; Female ; Male ; Mice ; Antigens, CD/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Gene Expression Profiling ; Helicobacter hepaticus/immunology ; Helicobacter Infections/immunology ; Helicobacter Infections/microbiology ; Immune Tolerance/immunology ; Inflammation/immunology ; Inflammation/microbiology ; Inflammation/pathology ; Integrin alpha Chains/metabolism ; Intestinal Mucosa/cytology ; Intestinal Mucosa/immunology ; Macrophages/immunology ; Macrophages/metabolism ; Mice, Inbred C57BL ; Mucous Membrane/cytology ; Mucous Membrane/immunology ; Receptors, Immunologic/metabolism ; Receptors, Immunologic/immunology ; Single-Cell Gene Expression Analysis ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/cytology ; Transcriptome
    Chemical Substances alpha E integrins ; Antigens, CD ; Integrin alpha Chains ; MRC1 protein, mouse ; Ptpns1 protein, mouse ; Receptors, Immunologic
    Language English
    Publishing date 2024-04-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-024-07251-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

    Alvarez-Martinez, Marisol / Cox, Luke S / Pearson, Claire F / Branchett, William J / Chakravarty, Probir / Wu, Xuemei / Slawinski, Hubert / Al-Dibouni, Alaa / Samelis, Vasileios A / Gabryšová, Leona / Priestnall, Simon L / Suárez-Bonnet, Alejandro / Mikolajczak, Anna / Briscoe, James / Powrie, Fiona / O'Garra, Anne

    Nature immunology

    2024  Volume 25, Issue 5, Page(s) 886–901

    Abstract: Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified ... ...

    Abstract Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4
    MeSH term(s) Animals ; Positive Regulatory Domain I-Binding Factor 1/genetics ; Positive Regulatory Domain I-Binding Factor 1/metabolism ; Mice ; Proto-Oncogene Proteins c-maf/genetics ; Colitis/immunology ; Colitis/genetics ; Mice, Knockout ; Humans ; Helicobacter hepaticus/immunology ; Helicobacter Infections/immunology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Intestinal Mucosa/microbiology ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/genetics ; Gene Expression Regulation ; Disease Models, Animal
    Chemical Substances Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-) ; Proto-Oncogene Proteins c-maf ; Prdm1 protein, mouse ; Maf protein, mouse
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-024-01814-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Microbiome diversity protects against pathogens by nutrient blocking.

    Spragge, Frances / Bakkeren, Erik / Jahn, Martin T / B N Araujo, Elizete / Pearson, Claire F / Wang, Xuedan / Pankhurst, Louise / Cunrath, Olivier / Foster, Kevin R

    Science (New York, N.Y.)

    2023  Volume 382, Issue 6676, Page(s) eadj3502

    Abstract: The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial ... ...

    Abstract The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.
    MeSH term(s) Animals ; Humans ; Mice ; Gastrointestinal Microbiome ; Nutrients/metabolism ; Host-Pathogen Interactions ; Klebsiella pneumoniae/genetics ; Klebsiella pneumoniae/growth & development ; Klebsiella pneumoniae/metabolism ; Salmonella typhimurium/genetics ; Salmonella typhimurium/growth & development ; Salmonella typhimurium/metabolism ; Symbiosis ; Germ-Free Life ; Klebsiella Infections/microbiology ; Salmonella Infections/microbiology ; Escherichia coli/genetics ; Escherichia coli/metabolism
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adj3502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4

    Hogan, Thea / Nowicka, Maria / Cownden, Daniel / Pearson, Claire F / Yates, Andrew J / Seddon, Benedict

    eLife

    2019  Volume 8

    Abstract: Laboratory mice develop populations of circulating memory ... ...

    Abstract Laboratory mice develop populations of circulating memory CD4
    MeSH term(s) Animals ; Antigens/immunology ; CD4-Positive T-Lymphocytes/immunology ; Immunologic Memory/immunology ; Mice ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antigens
    Language English
    Publishing date 2019-11-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.48901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Evidence of STAT5-dependent and -independent routes to CD8 memory formation and a preferential role for IL-7 over IL-15 in STAT5 activation.

    Kemp, Roslyn A / Pearson, Claire F / Cornish, Georgina H / Seddon, Benedict P

    Immunology and cell biology

    2009  Volume 88, Issue 2, Page(s) 213–219

    Abstract: Interleukin (IL)-7 and IL-15 have non-redundant roles in promoting development of memory CD8(+) T cells. STAT5 is activated by receptors of both cytokines and has also been implicated as a requirement for generation of memory. To determine whether STAT5 ... ...

    Abstract Interleukin (IL)-7 and IL-15 have non-redundant roles in promoting development of memory CD8(+) T cells. STAT5 is activated by receptors of both cytokines and has also been implicated as a requirement for generation of memory. To determine whether STAT5 activity was required for IL-7 and IL-15-mediated generation of memory, we expressed either wild type (WT) or constitutively active (CA) forms of STAT5a in normal effector cells and then observed their ability to form memory in cytokine replete or deficient hosts. Receptor-independent CA-STAT5a significantly enhanced memory formation in the absence of either cytokine but did not mediate complete rescue. Interestingly, WT-STAT5a expression enhanced memory formation in a strictly IL-7-dependent manner, suggesting that IL-7 is a more potent activator of STAT5 than IL-15 in vivo. These data suggest that the non-redundant requirement for IL-7 and IL-15 is mediated through differential activation of both STAT5-dependent and STAT5-independent pathways.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Immunologic Memory/immunology ; Interleukin-15/immunology ; Interleukin-7/immunology ; Mice ; Mice, Transgenic ; Mutant Proteins/metabolism ; Phosphorylation ; Receptors, Antigen, T-Cell/immunology ; Receptors, Interleukin-7/metabolism ; Retroviridae/genetics ; STAT5 Transcription Factor/immunology ; Transduction, Genetic
    Chemical Substances Interleukin-15 ; Interleukin-7 ; Mutant Proteins ; Receptors, Antigen, T-Cell ; Receptors, Interleukin-7 ; STAT5 Transcription Factor ; Stat5a protein, mouse
    Language English
    Publishing date 2009-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.2009.95
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation.

    Kabat, Agnieszka M / Harrison, Oliver J / Riffelmacher, Thomas / Moghaddam, Amin E / Pearson, Claire F / Laing, Adam / Abeler-Dörner, Lucie / Forman, Simon P / Grencis, Richard K / Sattentau, Quentin / Simon, Anna Katharina / Pott, Johanna / Maloy, Kevin J

    eLife

    2016  Volume 5, Page(s) e12444

    Abstract: A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential ... ...

    Abstract A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) Treg cells. Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders.
    MeSH term(s) Animals ; Autophagy-Related Proteins ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Gene Deletion ; Inflammatory Bowel Diseases/pathology ; Mice ; Mice, Knockout ; T-Lymphocytes, Regulatory/immunology ; Th2 Cells/immunology
    Chemical Substances Atg16l1 protein, mouse ; Autophagy-Related Proteins ; Carrier Proteins
    Language English
    Publishing date 2016-02-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.12444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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