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Gene Review

Il12rb2  -  interleukin 12 receptor, beta 2

Mus musculus

Synonyms: A930027I18Rik, IL-12 receptor subunit beta-2, IL-12R subunit beta-2, IL-12R-beta-2, IL-12RB2, ...
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Disease relevance of Il12rb2


High impact information on Il12rb2


Biological context of Il12rb2


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].


  1. Lack of Il12rb2 signaling predisposes to spontaneous autoimmunity and malignancy. Airoldi, I., Di Carlo, E., Cocco, C., Sorrentino, C., Fais, F., Cilli, M., D'Antuono, T., Colombo, M.P., Colombo, M.P., Pistoia, V. Blood (2005) [Pubmed]
  2. 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. Ireland, D.D., Palian, B.M., Reiss, C.S. Viral Immunol. (2005) [Pubmed]
  3. 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. Zhang, G.X., Gran, B., Yu, S., Li, J., Siglienti, I., Chen, X., Kamoun, M., Rostami, A. J. Immunol. (2003) [Pubmed]
  4. 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. Kitani, A., Fuss, I.J., Nakamura, K., Schwartz, O.M., Usui, T., Strober, W. J. Exp. Med. (2000) [Pubmed]
  5. Delta 9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophila infection. Klein, T.W., Newton, C.A., Nakachi, N., Friedman, H. J. Immunol. (2000) [Pubmed]
  6. Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. Szabo, S.J., Dighe, A.S., Gubler, U., Murphy, K.M. J. Exp. Med. (1997) [Pubmed]
  7. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Presky, D.H., Yang, H., Minetti, L.J., Chua, A.O., Nabavi, N., Wu, C.Y., Gately, M.K., Gubler, U. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. A point mutation in the IL-12R beta 2 gene underlies the IL-12 unresponsiveness of Lps-defective C57BL/10ScCr mice. Poltorak, A., Merlin, T., Nielsen, P.J., Sandra, O., Smirnova, I., Schupp, I., Boehm, T., Galanos, C., Freudenberg, M.A. J. Immunol. (2001) [Pubmed]
  9. 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. Wu, C., Wang, X., Gadina, M., O'Shea, J.J., Presky, D.H., Magram, J. J. Immunol. (2000) [Pubmed]
  10. In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria. Sam, H., Stevenson, M.M. J. Immunol. (1999) [Pubmed]
  11. IL-12 receptor regulation in IL-12-deficient BALB/c and C57BL/6 mice. Galbiati, F., Rogge, L., Adorini, L. Eur. J. Immunol. (2000) [Pubmed]
  12. Endotoxin fails to induce IFN-gamma in endotoxin-tolerant mice: deficiencies in both IL-12 heterodimer production and IL-12 responsiveness. Balkhy, H.H., Heinzel, F.P. J. Immunol. (1999) [Pubmed]
  13. Salmonella infection does not increase expression and activity of the high affinity IL-12 receptor. Elhofy, A., Marriott, I., Bost, K.L. J. Immunol. (2000) [Pubmed]
  14. Differentiation of murine NK cells into distinct subsets based on variable expression of the IL-12R beta 2 subunit. Chakir, H., Camilucci, A.A., Filion, L.G., Webb, J.R. J. Immunol. (2000) [Pubmed]
  15. Nitric oxide preferentially induces type 1 T cell differentiation by selectively up-regulating IL-12 receptor beta 2 expression via cGMP. Niedbala, W., Wei, X.Q., Campbell, C., Thomson, D., Komai-Koma, M., Liew, F.Y. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Combined treatment with interleukin-12 and indomethacin promotes increased resistance in BALB/c mice with established Leishmania major infections. Li, J., Padigel, U.M., Scott, P., Farrell, J.P. Infect. Immun. (2002) [Pubmed]
  17. CD4+ Th1 cells induced by dendritic cell-based immunotherapy in mice chronically infected with Leishmania amazonensis do not promote healing. Vanloubbeeck, Y.F., Ramer, A.E., Jie, F., Jones, D.E. Infect. Immun. (2004) [Pubmed]
  18. Cutting edge: ectopic expression of the IL-12 receptor-beta 2 in developing and committed Th2 cells does not affect the production of IL-4 or induce the production of IFN-gamma. Heath, V.L., Showe, L., Crain, C., Barrat, F.J., Trinchieri, G., O'Garra, A. J. Immunol. (2000) [Pubmed]
  19. 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. Nishikomori, R., Usui, T., Wu, C.Y., Morinobu, A., O'Shea, J.J., Strober, W. J. Immunol. (2002) [Pubmed]
  20. Potent antitumor activity of interleukin-27. Hisada, M., Kamiya, S., Fujita, K., Belladonna, M.L., Aoki, T., Koyanagi, Y., Mizuguchi, J., Yoshimoto, T. Cancer Res. (2004) [Pubmed]
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