Disease relevance of IL21R

• Here we demonstrate that surface IL-21 receptor (R) is expressed at variable levels by chronic lymphocytic leukemia (CLL) B cells freshly isolated from 33 different patients [1].
• The decreased expression of IL-21R in SLE was significantly associated with nephritis and high titer anti-double-strand DNA antibody [2].
• The abnormalities of IL-21R signaling might contribute to the pathological features of SLE, such as B lymphocytopenia [2].
• Immunohistochemical staining demonstrated that IL-21R-positive cells were significantly increased in inflamed synovial tissues of RA patients compared with osteoarthritis (OA) and healthy controls [3].
• We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc) [4].

High impact information on IL21R

• Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis [5].
• As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation [4].
• In this study we examined whether intestinal epithelial cells express IL-21R and respond to IL-21 in IBD [6].
• Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells [1].
• We now investigate the basis for IL21R gene regulation in T cells [7].

Biological context of IL21R

• Moreover, phosphatase inhibitors that increased phosphorylation of Sp1 diminished IL-21R transcription [7].
• Real-time reverse transcription polymerase chain reaction showed that HTLV-I-infected cell lines and primary ATL cells expressed IL-21R mRNA [8].
• Total serum IgE levels were measured in all subjects and associated with IL21R SNPs [9].
• We analyzed all the exons of the human IL21R gene and its 5' flanking region for sequence variation [9].
• IL21R shows strong sequence homologies to the interleukin-4 receptor alpha chain gene (IL4RA) [9].

Anatomical context of IL21R

• IBD LPMC supernatants stimulate MMP secretion by intestinal fibroblasts, and this effect is partly inhibited by IL21R/Fc [10].
• RESULTS: Constitutive expression of IL-21R was seen in intestinal epithelial cells, but was higher in IBD patients than in controls [6].
• NK cell IFN-gamma production was dependent on distinct signals mediated by the IL-21R and the FcR and was abrogated in STAT1-deficient NK cells [11].
• Flow cytometric analysis confirmed that IL-21R was mainly expressed in freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial fluid, but decreased gradually in T cells 24 h after anti-CD3 stimulation [3].
• These data indicate that IL-21R is overexpressed in the inflamed synovial membrane and in peripheral blood or synovial fluid leukocytes of RA patients, and that IL-21 enhances local T-cell activation, proliferation and proinflammatory cytokine secretion [3].

Physical interactions of IL21R

• Although IL-21 binds to the IL-21R expressed on gamma(c)-deficient ED40515(-) cells, IL-21 is unable to transduce any intracytoplasmic signals [12].

Regulatory relationships of IL21R

• IL-21R expression was up-regulated following cell stimulation via surface CD40 [1].
• IL-21R was actively transcribed in YM cells, while BCL6 that was under the control of the IL-21R promoter was only moderately expressed at the mRNA and protein level [13].

Other interactions of IL21R

• High expression of IL-21 and/or IL-21R has been described in T cell-mediated inflammatory diseases characterized by defects of counterregulatory mechanisms [14].
• Decreased expression of interleukin-21 receptor on peripheral B lymphocytes in systemic lupus erythematosus [2].
• Thus, blockade of IL-21R signalling pathway may have a therapeutic potential in acute RA patients [3].
• The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma [13].

Analytical, diagnostic and therapeutic context of IL21R

• METHODS: IL21 receptor (IL21R) was evaluated in intestinal fibroblasts by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting [10].
• In this study using biosensor technique, the ligand-binding properties of IL-21R and gamma(c), which are presently poorly understood on a molecular level, were analyzed employing recombinant ectodomains of IL-21R and gamma(c) [15].
• METHODS: IL-21R was evaluated in intestinal samples of IBD patients and controls by immunohistochemistry and Western blotting [6].

References