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FLASH GENE
Symbol TSLP contributors: mct/npt - updated : 26-01-2013
HGNC name thymic stromal lymphopoietin
HGNC id 30743
Location 5q22.1      Physical location : 110.407.389 - 110.413.722
DNA
TYPE functioning gene
STRUCTURE 6.33 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • several NFKB binding sites located in the proximal region of the TSLP promoter are critical for TSLP modulation in intestinal epithelial cells
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2629 18.1 159 - 2009 19770269
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Nervousbrain    
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion in human breast milk
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 28-residue signal sequence
  • 6 cysteines and 2 N-glycosylation sites
  • secondary structure several predicted alpha-helical regions in TSLP, a structure characterizing many classical antimicrobial peptides (AMPs)
    HOMOLOGY
    Homologene
    FAMILY
  • B cell-stimulating factors family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    text
  • constitutively secreted by intestinal epithelial cells
  • basic FUNCTION
  • enhancing the dendritic cells maturation process
  • with IL7, use different mechanisms to regulate human CD4(+) T cell homeostasis
  • may be an important player in the acute phase of HIV-1 infection by creating an environment that is conducive for sustaining the small dose of the initial virus inoculum that crosses the mucosal barrier
  • induces tight junction protein claudin-7 via NF-kappaB in dendritic cells
  • plays an important role in extravillous trophoblast invasion and placentation in human early pregnancy
  • potential key mediator of both the initiation and maintenance of Th2 responsiveness and thereby the allergic inflammatory cascade
  • acts on multiple lineages, including dendritic cells (DCs), T cells, NKT cells, eosinophils, and mast cells, mediating proliferation and survival and linking innate and adaptive immune responses
  • epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human dendritic cells in a cell-autonomous manner
  • could elicit basophil responses in both IL3/IL3R-sufficient and -deficient environments
  • its expression may influence susceptibility to multiple allergic diseases by regulating basophil haematopoiesis
  • may regulate basophil haematopoiesis in the bone marrow
  • role for TSLP in promoting basophil haematopoiesis, peripheral basophilia and altering the functional capacity of basophils
  • its antimicrobial activity is primarily mediated by the C-terminal part of the protein
  • capable of activating dendritic cells to promote T helper (Th) 2 immune responses
  • induces the invasion of human trophoblasts and plays a role in embryo implantation
  • might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion
  • implicated in the development and progression of allergic diseases such as atopic dermatitis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IRF3 indeed activates the gene promoter of TSLP via IRF-binding sequences
  • TSLP/CRLF2 plays a significant role in the amplification of polarization and chemokine production, thereby contributing to allergic inflammation
  • both IL3 and TSLP can promote basophil maturation from bone-marrow-resident precursor cells and promote survival of mature basophils isolated from the periphery
  • can be expressed and produced through caspase-1 and NFKB in mast cells
  • cell & other
    REGULATION
    Other calcium regulates the level of TSLP through RIP2/caspase-1/NFKB/IKBKA signal
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to esophagitis, eosinophilic (See EOE2)
  • Variant & Polymorphism SNP A allele of rs1837253, associated with protection from asthma, atopic asthma, and airway hyperresponsiveness
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionfertilityfemale
    potential therapeutic target for recurrent spontaneous abortion
    immunologyinfectious 
    possibility of targeting TSLP as a strategy against mucosal HIV-1 transmission and/or TSLP as a potential modulator of antigen-specific immune responses induced by candidate vaccines delivered at these mucosal viral entry sites
    ANIMAL & CELL MODELS
  • in rhesus macaques inoculated with simian immunodeficiency virus (SIV) by the vaginal route, dramatic increases in TSLP expression and SIV replication in the vaginal tissues within the first 2 weeks after virus exposure