Disease relevance of Il12rb2

• Il12rb2 gene-deficient animals developed in the first year of life immune-complex mesangial glomerulonephritis with serum antinuclear antibodies [1].
• Interleukin (IL)-12 receptor beta1 or IL-12 receptor beta 2 deficiency in mice indicates that IL-12 and IL-23 are not essential for host recovery from viral encephalitis [2].
• Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system [3].
• Treatment of experimental (Trinitrobenzene sulfonic acid) colitis by intranasal administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1-mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptor beta2 chain downregulation [4].
• Delta 9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophila infection [5].

High impact information on Il12rb2

• These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-gamma production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor beta2 (IL-12Rbeta2) chain expression [4].
• Importantly, IL-4 and IFN-gamma were found to significantly modify IL-12 receptor beta 2 expression after T cell activation [6].
• IL-4 inhibited IL-12R beta 2 expression leading to the loss of IL-12 signaling, providing an important point of regulation to promote commitment to the Th2 pathway [6].
• IL-12R beta 2 is not expressed by naive resting CD4+ T cells, but is induced upon antigen activation through the T cell receptor [6].
• Human and mouse IL-12R beta 2 proteins show a 68% amino acid sequence identity [7].

Biological context of Il12rb2

• Lack of Il12rb2 signaling predisposes to spontaneous autoimmunity and malignancy [1].
• A point mutation in the IL-12R beta 2 gene underlies the IL-12 unresponsiveness of Lps-defective C57BL/10ScCr mice [8].
• IL-12 receptor beta 2 (IL-12R beta 2)-deficient mice are defective in IL-12-mediated signaling despite the presence of high affinity IL-12 binding sites [9].
• Furthermore, B6 but not A/J mice showed significant up-regulation of splenic IL-12R beta2 mRNA over basal levels by days 3 and 4, coincident with sustained up-regulation of splenic IFN-gamma mRNA levels on days 3-5 [10].
• IL-4 is not required for down-regulation of IL-12Rbeta2 transcripts and inhibition of Th1 development in mice pretreated with soluble protein, as shown by their reduction in IL-4-deficient BALB/c mice [11].

Anatomical context of Il12rb2

• The interleukin-12 receptor beta2 (Il12rb2) gene is silenced in tumor cells from different human B-cell malignancies as opposed to their normal counterparts [1].
• To determine the basis for this selective loss, we examined IL-12R beta 2 subunit expression during Th cell development in response to T cell treatment with different cytokines [6].
• Finally, levels of IL-12R beta 2 subunit mRNA and the percent composition of NK lymphocytes in the spleen were both decreased in endotoxin-tolerant mice relative to controls [12].
• After oral inoculation with Salmonella, the level of mRNA expression encoding IL-12 receptor beta2 (IL-12Rbeta2) subunit was diminished 12 h postinfection in the mesenteric lymph nodes and subsequently in the spleen [13].
• Differentiation of murine NK cells into distinct subsets based on variable expression of the IL-12R beta 2 subunit [14].

Associations of Il12rb2 with chemical compounds

• Nitric oxide preferentially induces type 1 T cell differentiation by selectively up-regulating IL-12 receptor beta 2 expression via cGMP [15].
• Although in vivo indomethacin treatment did not appear to influence IL-12 production in infected mice, cells from indomethacin-treated mice did express higher levels of IL-12Rbeta2, suggesting that prostaglandins may play a role in the loss of IL-12 responsiveness observed during nonhealing L. major infections [16].
• Given intralesionally to chronically infected mice, this treatment induced the upregulation of mRNA levels for IFN-gamma, the transcription factor T-box expressed in T cells, and IL-12 receptor beta 2 in CD4(+) T cells from the DLN and an increase in parasite-specific immunoglobulin G2a in the serum [17].

Regulatory relationships of Il12rb2

• Although Con A-activated splenocytes from IL-12R beta 2(-/-) mice still bind IL-12 with both high and low affinity, no IL-12-induced biological functions can be detected [9].
• Restimulation of Th2 cells expressing this ectopic IL-12R beta 2 in the presence of IL-12 led to levels of IL-4 production similar to those in control Th2 cells [18].

Other interactions of Il12rb2

• Con A-activated splenocytes of IL-12R beta 2(-/-) mice failed to produce IFN-gamma or proliferate in response to IL-12 stimulation [9].
• These results demonstrate that although mouse IL-12R beta 1 is the subunit primarily responsible for binding IL-12, IL-12R beta 2 plays an essential role in mediating the biological functions of IL-12 in mice [9].
• Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling [19].
• IL-27 is a novel IL-12 family member that plays a role in the early regulation of T helper cell 1 initiation, including induction of T-bet and IL-12 receptor beta 2 expression [20].

References