Disease relevance of IL12RB2

• However, although the level of IL-12R beta 2 for the HIV(+) PBMCs was normalized by PHA, rhIL-12 caused a further augmentation [1].
• The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies [2].
• Depressed IL-12-mediated signal transduction in T cells from patients with Sézary syndrome is associated with the absence of IL-12 receptor beta 2 mRNA and highly reduced levels of STAT4 [3].
• CONCLUSION: SNPs within the 5' flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy [4].
• Up-regulation of the IL-12 receptor beta 2 chain in Crohn's disease [5].

High impact information on IL12RB2

• IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering [2].
• Thus, it is possible that a primary IL-12 defect may lead to secondary deficiencies in expression of the genes for IL-12Rbeta2 and IFN-gamma, thus amplifying immune deficiency during HIV infection [6].
• In these patients, a significant change was found in TNFalpha mRNA, whereas changes in IL-12 receptor-beta2 and IL-10 mRNA showed a trend [7].
• Specifically, WKAH-derived spinal cord cells were unable to up-regulate the IL-12 receptor beta2 gene in response to IL-12 stimulation [8].
• Recently, we reported that activated T cells of these patients display a down-regulation of IL-12R beta2 chain, suggesting an early commitment toward Th2 phenotype [9].

Biological context of IL12RB2

• Assignment of IL12RB2 to human chromosome 1p31.3-->p31.2 between D1S230 and D1S198 [10].
• AIM: Polymorphisms in the 5' flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model [4].
• RESULTS: Several SNPs, including -1035A>G, -1023A>G, -650delG, and -465A>G, were detected within the 5' flanking region of IL12RB2 [4].
• The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells [4].
• CONCLUSIONS: The RNA editing of IL-12R beta2, 2451 C-to-U (Ala 604 Val) conversion causes impairment of the IL-12 signal cascade and the subsequent reduction in IFN-gamma production, resulting in the impaired down-regulation of IgE production [11].

Anatomical context of IL12RB2

• Furthermore, the effects of cytokines on IL-12R beta2 chain expression on CD4(+) T cells were investigated [12].
• In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased [13].
• Moreover, the production of IFN-gamma by NK cells was greatly enhanced when a small amount of interleukin-12 (IL-12) was added, and this synergistic effect was associated with increased expression of the IL-12 receptor beta2 [14].
• We have recently shown that the differential expression of the IL-12R beta 2 chain in Th1 and Th2 cells, as measured at the mRNA level, accounts for an important regulatory mechanism in the differentiation of the two cell subsets [15].
• Although IL-12R beta 2 was absent in freshly isolated PBMC and in cord blood cells, we were able to detect IL-12R beta 2 expression selectively in differentiated Th1 and T cytotoxic 1, but not Th2 or T cytotoxic 2 cells [15].

Associations of IL12RB2 with chemical compounds

• Allergen RIT increases IL-12 production and IL-12R beta2 chain expression and thus may convert cytokine production from Th2 to Th1 or Th0 type in allergic asthma [12].
• The IL-12 receptor beta2 subunit contains three tyrosine residues in its cytoplasmic domain [16].
• The level of IL-12R beta2 chain mRNA was also upregulated to 130% after 24 h incubation with 0.1 microg/mL ribavirin (P = 0.037), whereas the beta1 chain did not change significantly under these conditions [17].

Physical interactions of IL12RB2

• The present study demonstrates that Jak2 binds to the cytoplasmic membrane-proximal region of IL-12R beta 2, and box 2 motif and tyrosine residues in the cytoplasmic domain were not required for binding [18].

Regulatory relationships of IL12RB2

• T-bet induction correlated with IFN-gamma production and with augmentation of surface expressed IL-12 receptor beta2 [19].

Other interactions of IL12RB2

• However, coculture of phytohemagglutinin (PHA)-activated HIV(+) or HIV(-) PBMCs with rhIL-12 (but not IFN-gamma) increased IL-12R beta 2 expression on the cell surface of both populations [1].
• However, examination of mRNA showed that both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs when compared with HIV(-) PBMCs [1].
• The amino-terminus of Jak2 is necessary for association with IL-12R beta 2 [18].
• Furthermore, IL-12R beta2 mRNA expression in PBMC was detected by reverse-transcriptase polymerase chain reaction in 6 of 18 HAM/TSP patients, but not in any control patients [20].
• In addition, these samples showed an increased expression of IL-18 (p = 0.0003), IL-4 (p = 0.0055), and IL-12R beta 2 (p = 0.007) [21].

Analytical, diagnostic and therapeutic context of IL12RB2

• Allergen rush immunotherapy increases interleukin (IL)-12 production and IL-12 receptor beta2 chain expression in patients with allergic asthma [12].
• Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell surface as detected by flow cytometry [1].
• In situ hybridization revealed that approximately one-third of BAL T cells expressed mRNA transcripts encoding the IL-12R beta 2 subunit following allergen challenge [22].
• RESULTS: Sequence analysis of the cDNA clones representing IL-12R beta2 mRNA transcripts revealed a C-to-U conversion at nucleotide 2451 (Ala 604 Val) on exon 13 in some atopic patients [11].

References