Disease relevance of IL21

• IL-21 is a novel growth and survival factor in multiple myeloma and may represent a target for future therapy [1].
• Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease [2].
• In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease [2].
• METHODS: IL-21 was examined by Western blotting in whole mucosa and lamina propria mononuclear cells (LPMCs) from patients with CD, ulcerative colitis (UC), and controls [2].
• METHODS: The expression of IL-21R and IL-21 was analyzed by TaqMan real-time polymerase chain reaction (PCR) and in situ hybridization of synovial biopsy samples from patients with RA and osteoarthritis (OA) [3].

High impact information on IL21

• A catalyst for these phenomena is the increased responses to the cytokine IL-21, a mediator that regulates T cell turnover [4].
• In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3 [5].
• Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function [5].
• A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells [6].
• IL-21-treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3alpha antibody [6].

Biological context of IL21

• IL-21 signaling failed to stimulate CLL B-cell proliferation, but induced their apoptosis [7].
• In this study, we have studied IL-15- and IL-21-induced gene expression in human primary NK and T cells and the NK-92 cell line [8].
• IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response [8].
• Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses [9].
• Our data show that IL-21 modulates the phenotype of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands [10].

Anatomical context of IL21

• AIM: To investigate whether IL21 controls MMP production by intestinal fibroblasts [11].
• The potency of IL-21 was close to that of IL-6 in the OH-2 cell line [1].
• We therefore examined whether IL-21 controls CD4(+)CD25(+) T cell function [12].
• The biological role of IL-21 in the immune system is complex, as IL-21 has been shown to have the ability to both promote and inhibit immune responses [13].
• Initial studies have demonstrated that IL-21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells [13].

Associations of IL21 with chemical compounds

• The gamma(c) residues involved in IL-21 binding were defined by alanine-scanning mutational analysis [14].
• In this study, we found that IL-21, in the presence of physiological concentration of hydrocortisone (HC), has a significant impact on the functions of NK cells derived from umbilical cord blood (CB) populations [15].
• Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10 [16].
• TCR-induced IL-21 gene expression was inhibited by cyclosporin A and FK506 [17].
• An hIL-21 analog was designed to stabilize the region around helix C through the introduction of a segment grafted from hIL-4 [18].

Physical interactions of IL21

• Although IL-21 binds to the IL-21R expressed on gamma(c)-deficient ED40515(-) cells, IL-21 is unable to transduce any intracytoplasmic signals [19].

Regulatory relationships of IL21

• IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells [20].
• IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells [21].
• Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis [22].

Other interactions of IL21

• Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21 [11].
• Our results suggest that both IL-15 and IL-21 have an important role in activating the NK cell-associated innate immune response [23].
• IL-15, IL-18, and IL-21 have significant roles as activators of NK and T cell functions [23].
• We demonstrate here that in addition to activating IFN-gamma gene expression, IFN-alpha/beta and IL-12 enhance the mRNA expression of IL-21 in activated human T cells [20].
• In conclusion, our results suggest a novel role for IFN-alpha/beta in the regulation of IL-21 response [20].

Analytical, diagnostic and therapeutic context of IL21

• Fibroblasts were stimulated with IL21 and MMPs were evaluated by RT-PCR and western blotting [11].
• Interestingly, mRNA for IL-21 could not be detected by real-time PCR and in situ hybridization [24].
• IL-21-induced STAT3 activation was verified by immunoprecipitation and Western blotting with anti-phosphotyrosine Ab [8].
• Of note, IL-21 was not detectable by real-time PCR and in situ hybridization in the same samples in vivo as in vitro [3].
• Concerning the intracellular signalling pathways, IL-21 activated the phosphorylation of the signal transducers and activators of transcription (STAT)3 and STAT5 [25].

References