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FLASH GENE
Symbol ICOSLG contributors: mct - updated : 02-01-2017
HGNC name inducible T-cell co-stimulator ligand
HGNC id 17087
Location 21q22.3      Physical location : 45.646.723 - 45.660.834
Synonym name
  • cDNA sequence, expressed in brain, 60kDa, related to chicken CD80-like precursor
  • B7-like protein Gl50
  • B7 homolog 2
  • CD275 antigen
  • ICOS ligand precursor
    • Synonym symbol(s) KIAA0653, GL50, B7RP1, B7H2, ICOSL, CD275, LICOS, B7-H2, B7RP-1, B7RP1, ICOS-L, B7h
    DNA
    TYPE functioning gene
    STRUCTURE 24.47 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1188 - 309 - 2000 11023515
    6 - 2969 - 185 - 2000 11023515
    7 - 3168 - 217 - 2000 11023515
    7 - 3320 - 302 - 2000 11023515
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Nervousbrain    
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Respiratoryepithelial cell
    Urinarytubular cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one Ig-like C2-type (immunoglobulin-like) domain
  • one Ig-like V-type (immunoglobulin-like) domain
    • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • immunoglobulin superfamily, BTN/MOG family
  • B7 superfamily
    • CATEGORY signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • acting as a costimulatory signal for T-cell proliferation and cytokine secretion
  • inducing also B-cell proliferation and differentiation into plasma cells
  • may play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function
  • may facilitate progression of acute myeloid leukemia
  • ICOS-ICOSLG signal plays a direct role in proliferation and differentiation of thyroid follicular cells (TFC) and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue
  • ICOS/ICOSLG interaction is a central event in immunosuppression of tumor-associated memory CD4(+) T cells
  • ICOSLG blockade abrogates likely tolerance at the fetomaternal interface by enhancing CD8(+) effector response and reducing local immunomodulation mediated by CD8(+) regulatory T cells
  • potential functional link between ADAM17 and ICOSLG in controlling adaptive immune responses
  • beyond the role in promoting T-helper (TFH) cells development, ICOSLG is important for individual B cells to competitively participate in the germinal centre (GC) reaction and to develop into bone-marrow plasma cells (BMPCs)
  • may participate in antigen presentation by epithelial cells
  • plays a critical role in immune response
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    text positive regulation of activated T cell proliferation
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ICOSLG-CD28 interaction was essential for the costimulation of human T cells primary responses to allogeneic antigens and memory recall responses
  • TNFRSF13 negatively regulates ICOSLG expression on B cells
  • loss of TNFRSF13B leads to increased ICOSLG expression and expands T follicular helper (Tfh) and germinal center (GC) B cells
    • cell & other
    REGULATION
    Other up-regulated by TNF-alpha
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in patients with systemic lupus erythematosus
    constitutional     --over  
    of ICOS and ICOSLG in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) vs patients with hereditary neuropathies (HNs)
    Susceptibility
  • to Crohn disease
    • Variant & Polymorphism other
  • rs7282490 ICOSLG GG risk carriers associated with an ileal Crohn disease phenotype
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Icosl -/- mice are healthy and fertile but have a reduced IgG1 production and affinity maturation, indicating a defect in T cell responses. Also have impaired T and B-cell interaction and germinal center formation