Il12rb1

Summary

Gene Symbol: Il12rb1
Description: interleukin 12 receptor, beta 1
Alias: CD212, IL-12R[b], interleukin-12 receptor subunit beta-1, IL-12 receptor beta component, IL-12 receptor subunit beta-1, IL-12R subunit beta-1, IL-12R-beta-1, Interleukin-12 receptor beta-1 chain precursor (IL-12R-beta1) (Interleukin-12 receptor beta) (IL-12 receptor beta component)
Species: mouse
Products:     Il12rb1

Top Publications

  1. Lin Y, Tang Y, Zong H, Gu J, Deng W, Wang C, et al. Cyclin G associated kinase interacts with interleukin 12 receptor beta2 and suppresses interleukin 12 induced IFN-gamma production. FEBS Lett. 2007;581:5151-7 pubmed
    ..These results suggest that GAK associates with IL-12Rbeta2 and may play a role in regulating IL-12 signaling. ..
  2. Chua A, Chizzonite R, Desai B, Truitt T, Nunes P, Minetti L, et al. Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol. 1994;153:128-36 pubmed
  3. van de Vosse E, Lichtenauer Kaligis E, van Dissel J, Ottenhoff T. Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function. Immunogenetics. 2003;54:817-29 pubmed
    ..in whom genetic deficiencies have been identified in several key genes in the type-1 cytokine pathway, including IL12RB1, the gene encoding the beta1 chain of the IL-12 and IL-23 receptors...
  4. Afanasyeva M, Wang Y, Kaya Z, Stafford E, Dohmen K, Sadighi Akha A, et al. Interleukin-12 receptor/STAT4 signaling is required for the development of autoimmune myocarditis in mice by an interferon-gamma-independent pathway. Circulation. 2001;104:3145-51 pubmed
    ..In contrast, IFN-gamma plays a protective role. The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes. ..
  5. Eriksson U, Kurrer M, Sebald W, Brombacher F, Kopf M. Dual role of the IL-12/IFN-gamma axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN-gamma. J Immunol. 2001;167:5464-9 pubmed
    ..Although IL-12 mediates disease by induction/expansion of Th1-type cells, IFN-gamma production from these cells limits disease progression. ..
  6. Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, et al. The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. Nat Immunol. 2008;9:34-41 pubmed
    ..we show that the IFN-gamma-induced transcription factor IRF1 was essential in T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor beta1 subunit (IL-12Rbeta1)...
  7. Oppmann B, Lesley R, Blom B, Timans J, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715-25 pubmed
    ..Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells. ..
  8. Yosef N, Shalek A, Gaublomme J, Jin H, Lee Y, Awasthi A, et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature. 2013;496:461-8 pubmed publisher
    ..Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation. ..
  9. Chua A, Wilkinson V, Presky D, Gubler U. Cloning and characterization of a mouse IL-12 receptor-beta component. J Immunol. 1995;155:4286-94 pubmed
    ..Despite the higher affinity displayed by the moIL-12R beta in Ba/F3 cells, this receptor alone is not sufficient to transduce a signal, suggesting that another subunit is probably required to generate a functional moIL-12R complex. ..

More Information

Publications60

  1. Presky D, Yang H, Minetti L, Chua A, Nabavi N, Wu C, et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci U S A. 1996;93:14002-7 pubmed
    ..These results demonstrate that the functional high-affinity IL-12R is composed of at least two beta-type cytokine receptor subunits, each independently exhibiting a low affinity for IL-12. ..
  2. Wu C, Ferrante J, Gately M, Magram J. Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL-12Rbeta1 is an essential component of the functional mouse IL-12 receptor. J Immunol. 1997;159:1658-65 pubmed
  3. Langowski J, Zhang X, Wu L, Mattson J, Chen T, Smith K, et al. IL-23 promotes tumour incidence and growth. Nature. 2006;442:461-5 pubmed
    ..We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours. ..
  4. Zhang G, Yu S, Gran B, Li J, Siglienti I, Chen X, et al. Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis. J Immunol. 2003;171:4485-92 pubmed
    ..We conclude that in the absence of IL-12Rbeta1, APCs play a prominent regulatory role in the induction of autoantigen-specific Th2 cells. ..
  5. Curtsinger J, Agarwal P, Lins D, Mescher M. Autocrine IFN-? promotes naive CD8 T cell differentiation and synergizes with IFN-? to stimulate strong function. J Immunol. 2012;189:659-68 pubmed publisher
    ..Thus, IFN-? is not only an important CD8 T cell effector cytokine, it is an autocrine/paracrine factor whose contributions to differentiation vary depending on whether the response is supported by IL-12 or type I IFN. ..
  6. Collison L, Delgoffe G, Guy C, Vignali K, Chaturvedi V, Fairweather D, et al. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012;13:290-9 pubmed publisher
    ..This unconventional mode of signaling, distinct from that of other members of the IL-12 family, may broaden the spectrum and specificity of IL-35-mediated suppression. ..
  7. Ray A, Fountain J, Miller H, Cooper A, Robinson R. IL12Rβ1ΔTM is a secreted product of il12rb1 that promotes control of extrapulmonary tuberculosis. Infect Immun. 2015;83:560-71 pubmed publisher
    b>IL12RB1 is a human gene that is important for resistance to Mycobacterium tuberculosis infection...
  8. Jana M, Dasgupta S, Pal U, Pahan K. IL-12 p40 homodimer, the so-called biologically inactive molecule, induces nitric oxide synthase in microglia via IL-12R beta 1. Glia. 2009;57:1553-65 pubmed publisher
    ..This study delineates a new role of IL-12R beta 1 and IL-12R beta 2 for the expression of iNOS and production of NO in microglia that may participate in the pathogenesis of neuroinflammatory diseases. ..
  9. Chang J, Cho J, Lee S, Choi S, Ha S, Sung Y. IL-12 priming during in vitro antigenic stimulation changes properties of CD8 T cells and increases generation of effector and memory cells. J Immunol. 2004;172:2818-26 pubmed
    ..Together, our results suggest that IL-12 can serve as an important, but dispensable regulatory factor for the development of CD8 T cells, and IL-12 priming could be useful in many medical applications. ..
  10. Fairweather D, Yusung S, Frisancho S, Barrett M, Gatewood S, Steele R, et al. IL-12 receptor beta 1 and Toll-like receptor 4 increase IL-1 beta- and IL-18-associated myocarditis and coxsackievirus replication. J Immunol. 2003;170:4731-7 pubmed
    ..These findings have important implications not only for the pathogenesis of myocarditis, but for other autoimmune diseases triggered by viral infections. ..
  11. Yamada A, Miyazaki T, Lu L, Ono M, Ito M, Terada M, et al. Genetic basis of tissue specificity of vasculitis in MRL/lpr mice. Arthritis Rheum. 2003;48:1445-51 pubmed
    ..Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity. ..
  12. Musikacharoen T, Oguma A, Yoshikai Y, Chiba N, Masuda A, Matsuguchi T. Interleukin-15 induces IL-12 receptor beta1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. Blood. 2005;105:711-20 pubmed
    Interleukin-12 receptor beta1 (IL12RB1) is expressed on a variety of immune cells, including T and natural killer (NK) cells and macrophages, and is involved in innate and adaptive immune responses...
  13. Zhang G, Gran B, Yu S, Li J, Siglienti I, Chen X, et al. 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. J Immunol. 2003;170:2153-60 pubmed
  14. Robinson R, Khader S, Martino C, Fountain J, Teixeira Coelho M, Pearl J, et al. Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rbeta1 isoform that enhances DC migration. J Exp Med. 2010;207:591-605 pubmed publisher
    ..Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Deltatm that encodes the protein IL-..
  15. Satoh Takayama N, Vosshenrich C, Lesjean Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29:958-70 pubmed publisher
    ..RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces...
  16. Lochner M, Peduto L, Cherrier M, Sawa S, Langa F, Varona R, et al. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med. 2008;205:1381-93 pubmed publisher
  17. Vom Berg J, Prokop S, Miller K, Obst J, Kälin R, Lopategui Cabezas I, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med. 2012;18:1812-9 pubmed publisher
    ..The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits. ..
  18. Coers J, Vance R, Fontana M, Dietrich W. Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. Cell Microbiol. 2007;9:2344-57 pubmed
    ..pneumophila is more complex than previously appreciated, and involves the concerted action of cytokine and intracellular microbe sensor signalling pathways. ..
  19. Watanabe T, Kitani A, Murray P, Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 2004;5:800-8 pubmed
    ..Thus, CARD15 mutations may lead to disease by causing excessive T(H)1 responses. ..
  20. Slight S, Lin Y, Messmer M, Khader S. Francisella tularensis LVS-induced Interleukin-12 p40 cytokine production mediates dendritic cell migration through IL-12 Receptor ?1. Cytokine. 2011;55:372-9 pubmed publisher
    ..Together, these findings illustrate that IL-12p40 is induced rapidly in response to F. tularensis LVS and is required for DC migration through an IL-12R?1-IL-12(p40)(2) dependent mechanism. ..
  21. Chognard G, Bellemare L, Pelletier A, Domínguez Punaro M, Beauchamp C, Guyon M, et al. The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation. PLoS ONE. 2014;9:e89092 pubmed publisher
  22. Kurokawa M, Konno S, Takahashi A, Plunkett B, Rittling S, Matsui Y, et al. Regulatory role of DC-derived osteopontin in systemic allergen sensitization. Eur J Immunol. 2009;39:3323-30 pubmed publisher
    ..These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12. ..
  23. Slütter B, Pewe L, Kaech S, Harty J. Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus. Immunity. 2013;39:939-48 pubmed publisher
    ..Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV. ..
  24. Frisancho Kiss S, Nyland J, Davis S, Frisancho J, Barrett M, Rose N, et al. Sex differences in coxsackievirus B3-induced myocarditis: IL-12Rbeta1 signaling and IFN-gamma increase inflammation in males independent from STAT4. Brain Res. 2006;1126:139-47 pubmed
    ..Thus, IFN-gamma increases inflammation in males independent from STAT4. These results demonstrate that sex differences greatly influence viral replication and the severity of acute CVB3-induced myocarditis. ..
  25. Keppler S, Theil K, Vucikuja S, Aichele P. Effector T-cell differentiation during viral and bacterial infections: Role of direct IL-12 signals for cell fate decision of CD8(+) T cells. Eur J Immunol. 2009;39:1774-83 pubmed publisher
    ..Thus, direct IL-12 signaling to CD8(+) T cells determines the cell fate decision between short-lived effector cells and memory precursor effector cells, which is dependent on pathogen-induced local cytokine milieu. ..
  26. Bielinska A, Makidon P, Janczak K, Blanco L, Swanson B, Smith D, et al. Distinct pathways of humoral and cellular immunity induced with the mucosal administration of a nanoemulsion adjuvant. J Immunol. 2014;192:2722-33 pubmed publisher
  27. Codarri L, Gyülveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. ROR?t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12:560-7 pubmed publisher
    ..Thus, in contrast to all other known helper T cell-derived cytokines, GM-CSF serves a nonredundant function in the initiation of autoimmune inflammation regardless of helper T cell polarization. ..
  28. Yoshimoto T, Furuhata M, Kamiya S, Hisada M, Miyaji H, Magami Y, et al. Positive modulation of IL-12 signaling by sphingosine kinase 2 associating with the IL-12 receptor beta 1 cytoplasmic region. J Immunol. 2003;171:1352-9 pubmed
    ..These results suggest that SPHK2 associates with the IL-12Rbeta1 cytoplasmic region and probably plays a role in modulating IL-12 signaling. ..
  29. Miller H, Robinson R. Early control of Mycobacterium tuberculosis infection requires il12rb1 expression by rag1-dependent lineages. Infect Immun. 2012;80:3828-41 pubmed publisher
    b>IL12RB1 is essential for human resistance to Mycobacterium tuberculosis infection...
  30. Brahmachari S, Pahan K. Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide. J Immunol. 2009;183:2045-58 pubmed publisher
    ..This study, therefore, delineates an unprecedented biological function of p40(2) in the regulation of Foxp3 via IL-12Rbeta1-mediated NO production. ..
  31. Camoglio L, Juffermans N, Peppelenbosch M, te Velde A, ten Kate F, van Deventer S, et al. Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis. Eur J Immunol. 2002;32:261-9 pubmed
    ..These results demonstrate that IL-12p40, in contrast to IL-12p70, inhibits TNBS-induced colitis and IL-18 expression independent of IFN-gamma. ..
  32. Floss D, Mrotzek S, Klöcker T, Schröder J, Grötzinger J, Rose John S, et al. Identification of canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the intracellular domain of the interleukin 23 receptor. J Biol Chem. 2013;288:19386-400 pubmed publisher
    ..In summary, we characterized IL-23-dependent signal transduction with a focus on STAT3 phosphorylation and identified canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the IL-23R. ..
  33. Jana M, Mondal S, Jana A, Pahan K. Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. Immunology. 2014;141:549-63 pubmed publisher
    ..These studies delineate a novel biological function of IL-12 that is absent in IL-23 and other p40 family members. ..
  34. Russell T, Yan Q, Fan G, Khalifah A, Bishop D, Brody S, et al. IL-12 p40 homodimer-dependent macrophage chemotaxis and respiratory viral inflammation are mediated through IL-12 receptor beta 1. J Immunol. 2003;171:6866-74 pubmed
    ..Thus, Rbeta1 mediates p80-dependent macrophage chemotaxis and inhibition of the p80-Rbeta1 interaction may provide a novel anti-inflammatory strategy to manipulate the inflammation associated with asthma and respiratory viral infection...
  35. Oh J, Kurche J, Burchill M, Kedl R. TLR7 enables cross-presentation by multiple dendritic cell subsets through a type I IFN-dependent pathway. Blood. 2011;118:3028-38 pubmed publisher
  36. Rangachari M, Mauermann N, Marty R, Dirnhofer S, Kurrer M, Komnenovic V, et al. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med. 2006;203:2009-19 pubmed
    ..Collectively, these data show that severe IL-17-mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ. ..
  37. Kim D, Youn J, Seo S, Jin H, Sung Y. Differential regulation of antigen-specific CD8+ T cell responses by IL-12p40 in a dose-dependent manner. J Immunol. 2008;180:7167-74 pubmed
    ..Our findings provide a novel insight on the physiological role of IL-12p40, which can be informative in the design of vaccine strategies and therapeutic regimens. ..
  38. de Souza C, Morel L, Cabrera W, Starobinas N, Ribeiro O, Siqueira M, et al. Quantitative trait loci in Chromosomes 3, 8, and 9 regulate antibody production against Salmonella flagellar antigens in the mouse. Mamm Genome. 2004;15:630-6 pubmed
    ..HIII and LIII lines differ in the resistance to several diseases, therefore, the relevance of these QTL with the genetic factors involved in infections, autoimmunity, and neoplastic disease progression is discussed. ..
  39. Piccotti J, Li K, Chan S, Eichwald E, Bishop D. Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor. Transplantation. 1999;67:1453-60 pubmed
    ..Further, these data indicate that IL-12Rbeta1 is essential for the enhancement of both in vitro and in vivo alloimmune responses by exogenous IL-12. ..
  40. Zou J, Presky D, Wu C, Gubler U. Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases. J Biol Chem. 1997;272:6073-7 pubmed
  41. Richer M, Nolz J, Harty J. Pathogen-specific inflammatory milieux tune the antigen sensitivity of CD8(+) T cells by enhancing T cell receptor signaling. Immunity. 2013;38:140-52 pubmed publisher
    ..Dynamic tuning of CD8(+) T cell antigen sensitivity by inflammatory cytokines most likely optimizes immunity to specific pathogens while minimizing the risk of immunopathology at steady state. ..
  42. Gyülveszi G, Haak S, Becher B. IL-23-driven encephalo-tropism and Th17 polarization during CNS-inflammation in vivo. Eur J Immunol. 2009;39:1864-9 pubmed publisher
  43. Poltorak A, Merlin T, Nielsen P, Sandra O, Smirnova I, Schupp I, et al. A point mutation in the IL-12R beta 2 gene underlies the IL-12 unresponsiveness of Lps-defective C57BL/10ScCr mice. J Immunol. 2001;167:2106-11 pubmed
    ..Because the phosphorylation of STAT4 is a prerequisite for the IL-12-mediated induction of IFN-gamma, its absence in Cr mice is responsible for their defective IFN-gamma response to microorganisms. ..
  44. Freudenberg M, Merlin T, Kalis C, Chvatchko Y, Stübig H, Galanos C. Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling. J Immunol. 2002;169:1665-8 pubmed
    ..This pathway participates in the induction of IFN-gamma by Gram-negative bacteria and is therefore expected to play a role whenever IFN-alpha or IFN-beta and IL-18 are produced concomitantly during bacterial, viral, or other infections. ..
  45. Li J, Gran B, Zhang G, Ventura E, Siglienti I, Rostami A, et al. Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci. 2003;215:95-103 pubmed
    ..Thus, IL-23 produced by CNS microglia/macrophages may contribute to the early induction of EAE. In the CNS, IL-23 may preferentially target infiltrating mononuclear cells, which upregulate IL-23R, rather than parenchymal microglia. ..
  46. Fairweather D, Frisancho Kiss S, Yusung S, Barrett M, Davis S, Gatewood S, et al. Interferon-gamma protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-beta 1, interleukin-1 beta, and interleukin-4 in the heart. Am J Pathol. 2004;165:1883-94 pubmed
  47. Rowe J, Ertelt J, Way S. Innate IFN-? is essential for programmed death ligand-1-mediated T cell stimulation following Listeria monocytogenes infection. J Immunol. 2012;189:876-84 pubmed publisher
    ..Thus, innate IFN-? is essential for PDL-1-mediated T cell stimulation. ..
  48. Xiao Z, Mescher M, Jameson S. Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation. J Exp Med. 2007;204:2667-77 pubmed
    ..g., infected cells), while limiting collateral damage to bystander cells. ..
  49. Vogel L, Showe L, Lester T, McNutt R, Van Cleave V, Metzger D. Direct binding of IL-12 to human and murine B lymphocytes. Int Immunol. 1996;8:1955-62 pubmed
    ..These findings indicate that B cells represent another major target for IL-12 in addition to T and NK cells, and that IL-12 can directly affect humoral immunity. ..
  50. Jana M, Pahan K. IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in microglia and macrophages. Mol Immunol. 2009;46:773-83 pubmed publisher
    ..These results delineate a novel biological function of p40(2) and raise the possibility that biological function of IL-12 p40(2) may be different from IL-12 p70. ..
  51. Sandau M, Winstead C, Jameson S. IL-15 is required for sustained lymphopenia-driven proliferation and accumulation of CD8 T cells. J Immunol. 2007;179:120-5 pubmed
    ..These findings demonstrate that cytokine requirements for LIP change during the process itself, illustrating the need to identify factors that regulate successive stages of lymphopenia-driven proliferation. ..