ArticleProceedings of the National Academy of Sciences of the United States of America2009
A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 44 citations in OpenAlex.
- Lymphocyte-mediated immune responses to Leishmania infection.Nature reviews. Immunology · 2026Review
- A scalable two-step genome editing strategy for generating full-length gene-humanized mice at diverse genomic loci.Nature communications · 2026Article
- Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model.Vascular pharmacology · 2024Article
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- IL-10-producing Th1 cells possess a distinct molecular signature in malariaThe Journal of clinical investigation · 2023Article
- Principles of Genetic Engineering.Genes · 2020Review
- The host cell secretory pathway mediates the export of Leishmania virulence factors out of the parasitophorous vacuole.PLoS pathogens · 2019Article
- miR-132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity.EMBO reports · 2019Article
- IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly inFrontiers in immunology · 2019Article
- HIF-1α hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis.Scientific reports · 2018Article
- Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis.Wellcome open research · 2018Article
- What do we know about the role of regulatory B cells (Breg) during the course of infection of two major parasitic diseases, malaria and leishmaniasis?Pathogens and global health · 2017Review
- IRF-5-Mediated Inflammation Limits CD8+ T Cell Expansion by Inducing HIF-1α and Impairing Dendritic Cell Functions during Leishmania Infection.PLoS pathogens · 2015Article
- Review
- A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.PLoS computational biology · 2013Article
- A protective role for human IL-10-expressing CD4+ T cells in colitis.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Differential Regulation of the Immune Response in the Spleen and Liver of Mice Infected with Leishmania donovani.Journal of tropical medicine · 2012Article
- Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection.PLoS neglected tropical diseases · 2012Article
- IL-10-producing Th1 cells and disease progression are regulated by distinct CD11c⁺ cell populations during visceral leishmaniasis.PLoS pathogens · 2012Article
- Leishmaniasis: complexity at the host-pathogen interface.Nature reviews. Microbiology · 2011Review
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10 authors at 4 institutions in 1 country.
Funding
Abstract
Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by diverse cell populations. Studies in mice suggest that the cellular source of IL-10 is a key determinant in various disease pathologies, yet little is known regarding the control of tissue-specific human IL-10 expression. To assess cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC) in which the IL10 gene is positioned centrally. Since human IL-10 is biologically active in the mouse, we could examine the in vivo capacity of tissue-specific human IL-10 expression to recapitulate IL-10-dependent phenotypes by reconstituting Il10(-/-) mice (Il10(-/-)/hIL10BAC). In response to LPS, Il10(-/-)/hIL10BAC mice proficiently regulate IL-10-target genes and normalize sensitivity to LPS toxicity via faithful human IL-10 expression from macrophages and dendritic cells. However, in the Leishmania donovani model of pathogen persistence, Il10(-/-)/hIL10BAC mice did not develop the characteristic IL-10(+)IFN-gamma(+)CD4 T cell subset thought to mediate persistence and, like Il10(-/-) mice, cleared the parasites. Furthermore, the IL-10-promoting cytokine IL-27 failed to regulate transgenic human IL-10 production in CD4(+) T cells in vitro which together suggests that the hIL10BAC encodes for weak T cell-specific IL-10 expression. Thus, the hIL10BAC mouse is a model of human gene structure and function revealing tissue-specific regulatory requirements for IL-10 expression which impacts disease outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.