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FLASH GENE
Symbol IL21 contributors: mct - updated : 10-04-2019
HGNC name interleukin 21
HGNC id 6005
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivemale systemtestis   
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunenatural killer Homo sapiens
Lymphoid/ImmuneT cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
Homologene
FAMILY
  • IL-15/IL-21 family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text
  • IL21 is mainly produced from activated CD4+ T cells and natural killer T (NKT) cells
  • basic FUNCTION
  • involved in the cross-talk between epithelial and immune cells in the gut
  • has pleiotropic actions, from augmenting the proliferation of T cells and driving the differentiation of B cells into memory cells and terminally differentiated plasma cells to augmenting the activity of natural killer cells
  • serves as a critical helper factor that is required for viral control in CD8+ T cells
  • acts directly on B cells and cooperates with TLR signaling for optimal B cell responses
  • plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (T(FH)) cells
  • IL21 and CD40LG collaborate through at least two distinct mechanisms to synergistically promote PRDM1 activation and plasma cells (PCs) differentiation
  • IL21 and CSF2 exhibit cross-regulatory actions on gene regulation and apoptosis, regulating conventional dendritic cells (cDCs) numbers and thereby the magnitude of the immune response
  • IL21 suppresses the development of Th2 cells and functions of polarized Th2 cells
  • critical role of IL21 in breaking immune homeostasis in aplastic anemia (AA) by promoting Th17 cells, activating BM T cells and suppressing Tregs
  • is a type I cytokine essential for immune cell differentiation and function
  • IL21 exerts major effects on B-cell activation and differentiation or apoptosis during humoral immune responses and induces differentiation of na
  • ve B cells and memory B cells into plasma cells
  • IL21 modulates the effector functions of T, B and NK cells, which not only have key roles in antitumoral and antiviral immunity but also in exerting major effects on inflammatory responses promoting the development of autoimmune diseases
  • context-dependent role for IL21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and functions
  • IL21 may link immune responses to physiological or pathological platelet-dependent processes
  • regulates megakaryocyte development and platelet homeostasis
  • IL21 reinforces humoral immunity by restricting T follicular regulatory (Tfr) cell proliferation
  • is crucial for the development of a robust CD8+ T cell response and has been shown to promote antitumor immunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • IL21/IL21R pathway is a critical component of the memory B cell response
  • IL21 signaling has an intrinsic role in promoting the protective capacity of T cells
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • link between IL21-induced JAK/STAT signaling, MYC regulation, and differentiation of human B cells
  • IL21 drives CD8(+) CTL differentiation via the actions of the transcription factor TBX21
  • role for IL21 as an inducer of the costimulatory ligand CD86 on B lymphocytes
  • IL21 is an inducer of IL22 production in CD4+ T cells
  • STAT1 and STAT3 have at least partially opposing roles in IL21 signaling in CD4(+) T cells
  • interplay between STAT1 and STAT3 in fine-tuning IL21 actions
  • IL6 is a master regulator of IL21 in effector CD8+ T cells
  • is produced predominantly by activated CD4+ T cells and has pleiotropic effects on immunity via IL21R
  • IL4 and IL21 cooperate to induce the high BCL6 protein level required for germinal center formation
  • PTPN11 is involved in the IL21-mediated ERK1/2 activation and cell proliferation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CVID11
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    IL21 and IL21R expression in lymphocytes and neurons in multiple sclerosis brain
    tumoral     --low  
    in osteosarcoma patients
    Susceptibility to systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP
  • both IL21 rs907715 and rs2221903 polymorphisms may be associated with SLE susceptibility
  • Candidate gene
    Marker
  • IL21 is a candidate biomarker of resistance to tuberculosis
  • Therapy target
    ANIMAL & CELL MODELS