Disease relevance of Il21

• Interleukin-21 inhibits dendritic cell-mediated T cell activation and induction of contact hypersensitivity in vivo [1].
• Expression, purification and identification of recombinant mouse interleukin 21 protein in E. coli [2].
• Treatment of tumor-bearing mice with IL-21 plasmid DNA significantly inhibited the growth of B16 melanoma and MCA205 fibrosarcoma in a dose-dependent manner without significant toxicity and increased the survival rate, compared with mice treated with control plasmid DNA [3].
• IL-21 and IL-15 expression plasmids were intravenously injected under high pressure into the tail veins of mice, which were subsequently challenged by an intravenous injection of RLmale1 lymphoma cells [4].
• In a series of experimental and spontaneous metastases models in mice, we demonstrate far superior antitumor activity of the alpha-GalCer/IL-21 combination above either agent alone [5].
• Mice genetically deficient for Id2 were completely unsusceptible to IL-21-induced prevention of IgE CSR and anaphylaxis [6].
• From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach [7].
• We show that IL-21- and IL-21R-deficient mice are highly susceptible to experimental autoimmune encephalomyelitis with disease scores that were comparable, or even higher at the peak of disease, to those of control mice [8].

High impact information on Il21

• In this issue of Cell, evidence is provided that this homeostatic proliferation, coupled with excess production of a cytokine, IL-21, is a key factor in susceptibility to autoimmune diabetes [9].
• Furthermore, IL-21 blocked IL-15-induced expansion of resting NK cells, thus preventing the initiation of further innate responses [10].
• Mice lacking IL-21R (IL-21R(-/-)) had normal NK cell development but no detectable responses to IL-21 [10].
• We now report that IL-21, a product of activated T cells, may serve this function [10].
• IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity [10].

Chemical compound and disease context of Il21

• Using a recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse challenge model, we observed that IL-21 plasmid produced sustained resistance to viral transmission when injected 5 days after DNA vaccination [11].
• Specifically, IL-21 only demonstrated a therapeutic effect in mice challenged with a retinoic acid early inducible-1delta-bearing lymphoma but not in mice bearing parental RMA tumors lacking NKG2D ligands [12].

Biological context of Il21

• Although B cell subsets expressed somewhat varied levels of the IL-21 receptor, LPS-stimulated follicular and marginal B cell subsets were also dominantly susceptible to IL-21-induced growth arrest and cell death [13].
• Our data demonstrate that IL-21 is a new modulator of DC-T cell interaction with the potential to induce DC-mediated antigen-specific tolerance [1].
• In order to study the biological functions of IL-21, we constructed a mIL-21 prokaryotic expression plasmid and expressed the recombinant mIL-21 protein in E. coli in present study [2].
• IL-21 is capable of co-stimulating mature T cells, B cells, NK cells, and of stimulating CD16 expression on the surface of NK cells to induce ADCC in innate immune response [2].
• In addition, the activation of primary B cells with IL-4, LPS, or anti-CD40 Ab does not prevent IL-21-mediated apoptosis [14].

Anatomical context of Il21

• IL-21 is produced by activated T cells, and it influences proliferation of T and B cells and cytolytic activity of natural killer cells [15].
• We here analyzed the role of IL-21 in dendritic cell (DC)-induced, T cell-mediated contact hypersensitivity (CHS) in vivo and on T cell activation and unspecific mixed lymphocyte reaction in vitro [1].
• However, the role of this transcription factor in IL-15- and IL-21-stimulated murine bone marrow (BM) cells is unclear [16].
• IL-21 significantly elevated the cytotoxic T lymphocyte activity in the spleens of tumor-inoculated mice, while the two cytokines augmented NK killing activity in a synergistic manner [4].
• Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells [17].

Associations of Il21 with chemical compounds

• Interestingly, 2h incubation of these DC with IL-21 before injection completely inhibited the potential of these DC to induce a CHS reaction to the hapten fluorescein 5-isothiocyanate in vivo [1].

Physical interactions of Il21

• Stat3 can directly bind the Il21 promoter [18].

Regulatory relationships of Il21

• Functional studies demonstrated that IL-21 substantially inhibited proliferation and induced Bim-dependent apoptosis for LPS or CpG DNA-activated B cells [19].
• In this study, we demonstrate that in certain tumor models IL-21-enhanced tumor rejection is NKG2D dependent [12].
• IL-21 induces tumor rejection by specific CTL and IFN-gamma-dependent CXC chemokines in syngeneic mice [20].
• 1. Coinciding with these cellular changes IL-21 enhances cytolytic capacity across a spectrum of target sensitivities and induces IL-10 and IFN-gamma production [21].
• In support of the latter possibility, we report that the recently described cytokine IL-21 can markedly enhance the proliferation of immature (and mature) NK cells in the presence of doses of IL-2 and IL-15 that by themselves have little growth-promoting activity [22].

Other interactions of Il21

• IL-21 distinctively regulates B cell growth and death, and it redundantly functions with IL-4 for IgG production [13].
• Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses [15].
• Mouse IL-21 cDNA was amplified from Con A-activated mouse T cells by RT-PCR [23].
• To determine whether IL-21 has broad immunoregulatory activity and can stimulate durable antitumour responses, we constructed mouse IL-21 (mIL-21) recombinant plasmid and evaluated its antitumor efficacy [23].
• Differential effects of IL-15 and IL-21 in myeloid (CD11b+) and lymphoid (CD11b-) bone marrow cells [16].

Analytical, diagnostic and therapeutic context of Il21

• By PCR, we demonstrate here constitutive expression of the specific IL-21 receptor and the common gamma-chain in DC, which together are able to mediate IL-21 signaling [1].
• Thus, IL-21 is a potential useful therapeutic molecule for immunotherapy of malignancies, by eliciting innate and adaptive anti-tumor responses in tumor-bearing hosts [2].
• Preliminary study on mouse interleukin-21 application in tumor gene therapy [23].
• Mouse IL-21 expression was analyzed by Western blotting and its activities were detected by 3H-TdR incorporation and MTT assay [23].
• Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion [24].

References