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FLASH GENE
Symbol IL21 contributors: mct - updated : 10-04-2019
HGNC name interleukin 21
HGNC id 6005
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