The Immunological Genome Project: networks of gene expression in immune cells

Heng, Tracy; Painter, Michio W.; Elpek, Kutlu G.; Lukacs‐Kornek, Veronika; Mauermann, Nora; Turley, Shannon J.; Koller, Daphne; Kim, Francis S.; Wagers, Amy J.; Asinovski, Natasha; Davis, Scott; Fassett, Marlys S.; Feuerer, Markus; Gray, Daniel H.D.; Haxhinasto, Sokol; Hill, Jonathan A.; Hyatt, Gordon; Laplace, Catherine; Leatherbee, Kristen; Mathis, Diane; Benoist, Christophe; Jianu, Radu; Laidlaw, David H.; Best, J Adam; Knell, Jamie; Goldrath, Ananda W.; Jarjoura, Jessica; Sun, Joseph C.; Zhu, Yanan; Lanier, Lewis L.; Ergün, Ayla; Zheng, Li; Collins, James J.; Shinton, Susan A.; Hardy, Richard R.; Friedline, Randall H.; Sylvia, Katelyn; Kang, Joonsoo

doi:10.1038/ni1008-1091

Cited by 1,519 publications

(1,481 citation statements)

References 18 publications

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“…Previous work by Petrie and colleagues showed that IL-1β and IL-23 are expressed by mTECs at comparable levels to IL-7 42 . Moreover, specific subsets of thymic γδ T cells and a population of CD4 + T cells express high levels of IL-21R, during the appropriate ontological window of time to affect γδ17 development (www.immgen.org) 43 , plus a subset of IL-21 expressing thymocytes was recently reported 44 . Therefore, we assessed whether inhibiting IL-1β, IL21, and IL-23 inputs would interfere with the generation of γδ17 cells in the context of wildtype progenitors in the fetal thymus.…”

Section: Resultsmentioning

confidence: 99%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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γδ T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2−/− T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNγ versus IL-17 producing γδ T cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL-1β, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNγ and IL-17 producing γδ T-cell subsets.

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Section: Resultsmentioning

confidence: 99%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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“…Transcripts with the highest level of expression increased in both ALS and aging were compared with data generated by the Immunological Genome (ImmGen) project, a consortium that has mapped gene expression patterns in major classes of immune cell types (Heng & Painter, 2008). The purpose of this analysis was to understand the cellular basis underlying the increased immune and inflammatory response during aging and ALS.…”

Section: Resultsmentioning

confidence: 99%

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

et al. 2018

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SIRT1 is an NAD+‐dependent deacetylase that functions in a variety of cells and tissues to mitigate age‐associated diseases. However, it remains unknown if SIRT1 also acts to prevent pathological changes that accrue in motor neurons during aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1 expression decreases in the spinal cord of wild‐type mice during normal aging. Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we found that SIRT1 slows age‐related degeneration of motor neurons’ presynaptic sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord shows an overlap of greater than 90% when comparing alterations during normal aging with changes during ALS, revealing a substantial upregulation in immune and inflammatory response genes and a downregulation of synaptic transcripts. In addition, overexpressing SIRT1 in motor neurons delays progression to end‐stage disease in high copy SOD1G93A mice. Thus, our findings suggest that there are parallels between ALS and aging, and interventions to impede aging may also slow the progression of this devastating disease.

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“…ImmGen, initiated in 2007, is a collaborative group of 15 immunology and computational biology laboratories that have sought to perform, under carefully standardized conditions, a thorough dissection of gene expression in the immune system 7 . In the first phase, the group focused on generating gene expression profiles for primary haematopoietic cells from different anatomical locations that were analysed directly ex vivo at finely defined stages of differentiation.…”

Section: The Consmentioning

confidence: 99%

Consortium biology in immunology: the perspective from the Immunological Genome Project

Benoist¹,

Lanier²,

Mérad³

et al. 2012

Nat Rev Immunol

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The Immunological Genome Project: networks of gene expression in immune cells

Abstract: The Immunological Genome Project combines immunology and computational biology laboratories in an effort to establish a complete 'road map' of gene-expression and regulatory networks in all immune cells.

Cited by 1,519 publications

References 18 publications

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

Consortium biology in immunology: the perspective from the Immunological Genome Project

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