Genomes and Genes
Gene Symbol: Il12b
Description: interleukin 12b
Alias: Il-12b, Il-12p40, Il12p40, p40, interleukin-12 subunit beta, CLMF p40, IL-12 p40 subunit, IL-12 subunit p40, IL-23 subunit p40, cytotoxic lymphocyte maturation factor 40 kDa subunit, interleukin-12 p40 subunit
- Ghilardi N, Kljavin N, Chen Q, Lucas S, Gurney A, De Sauvage F. Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice. J Immunol. 2004;172:2827-33 pubmed..heterodimeric cytokine IL-23 consists of a private cytokine-like p19 subunit and a cytokine receptor-like subunit, p40, which is shared with IL-12...
- Zhu C, Rao K, Xiong H, Gagnidze K, Li F, Horvath C, et al. Activation of the murine interleukin-12 p40 promoter by functional interactions between NFAT and ICSBP. J Biol Chem. 2003;278:39372-82 pubmed..The IL-12 p40 gene product, expressed specifically in macrophages and dendritic cells, heterodimerizes with p35 to form bioactive ..
- Gran B, Zhang G, Yu S, Li J, Chen X, Ventura E, et al. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol. 2002;169:7104-10 pubmed..IL-12 is a heterodimeric cytokine, composed of a p40 and a p35 subunit, which is thought to play an important role in the development of Th1 cells and can exacerbate ..
- Kinjo Y, Kawakami K, Uezu K, Yara S, Miyagi K, Koguchi Y, et al. Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12p40. J Immunol. 2002;169:323-9 pubmed..Taken together, our results indicate that IL-18 plays an important role in Th1 response and host defense against M. tuberculosis infection although the contribution was not as profound as that of IL-12p40. ..
- Kohyama S, Ohno S, Isoda A, Moriya O, Belladonna M, Hayashi H, et al. IL-23 enhances host defense against vaccinia virus infection via a mechanism partly involving IL-17. J Immunol. 2007;179:3917-25 pubmed..Unveiling of an alternative pathway in the IL-23-regulated resistance might provide a novel strategy against infectious pathogens without side effects of autoimmunity. ..
- Luger D, Silver P, Tang J, Cua D, Chen Z, Iwakura Y, et al. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008;205:799-810 pubmed publisher..These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm. ..
- Chiaramonte M, Mentink Kane M, Jacobson B, Cheever A, Whitters M, Goad M, et al. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med. 2003;197:687-701 pubmed..Together, these studies illustrate the central role played by the IL-13Ralpha2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response. ..
- Cua D, Sherlock J, Chen Y, Murphy C, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-8 pubmedInterleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits...
- Nguyen K, Salazar Mather T, Dalod M, Van Deusen J, Wei X, Liew F, et al. Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol. 2002;169:4279-87 pubmed
- Pathak S, Basu S, Bhattacharyya A, Pathak S, Kundu M, Basu J. Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages. J Biol Chem. 2005;280:42794-800 pubmed..tuberculosis. We demonstrate that Man-LAM inhibits IL-12 p40 production mediated by subsequent challenge with lipopolysaccharide (LPS)...
- Pearce E, Shen H. Generation of CD8 T cell memory is regulated by IL-12. J Immunol. 2007;179:2074-81 pubmed..These results have implications for understanding memory T cell development and enhancing vaccine efficacy, and offer new insight into the role of IL-12 in coordinating the innate and adaptive immune response. ..
- Masumi A, Tamaoki S, Wang I, Ozato K, Komuro K. IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS Lett. 2002;531:348-53 pubmed..Together, these results indicate that ICSBP and IRF-1 cooperatively stimulate murine IL-12 transcription through a novel regulatory element in the murine promoter. ..
- Cooper A, Kipnis A, Turner J, Magram J, Ferrante J, Orme I. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J Immunol. 2002;168:1322-7 pubmed..To determine whether this is the case in tuberculosis, both p35 and p40 knockout mice were infected with Mycobacterium tuberculosis...
- Jana M, Dasgupta S, Saha R, Liu X, Pahan K. Induction of tumor necrosis factor-alpha (TNF-alpha) by interleukin-12 p40 monomer and homodimer in microglia and macrophages. J Neurochem. 2003;86:519-28 pubmedThe present study was undertaken to explore the role of interleukin-12 (IL-12) p40 in the expression of TNF-alpha in microglia...
- Yap G, Ortmann R, Shevach E, Sher A. A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute resistance to Toxoplasma gondii and rescue by IL-18 treatment. J Immunol. 2001;166:5720-5 pubmed..Q/J mice can result in defective host resistance and demonstrate a therapeutic function for IL-18 in reversing a genetically based immunodeficiency in IL-12-dependent IFN-gamma production. ..
- Wilson M, Elnekave E, Mentink Kane M, Hodges M, Pesce J, Ramalingam T, et al. IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest. 2007;117:2941-51 pubmed..Thus, IL-10 and IL-13Ralpha2 are both required to control chronic Th2-driven pathological responses. ..
- Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14:282-9 pubmed publisher..rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens...
- Schleicher U, Liese J, Knippertz I, Kurzmann C, Hesse A, Heit A, et al. NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. J Exp Med. 2007;204:893-906 pubmed
- Khader S, Bell G, Pearl J, Fountain J, Rangel Moreno J, Cilley G, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol. 2007;8:369-77 pubmed
- Skokos D, Nussenzweig M. CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J Exp Med. 2007;204:1525-31 pubmed..Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways. ..
- Robinson R, Khader S, Locksley R, Lien E, Smiley S, Cooper A. Yersinia pestis evades TLR4-dependent induction of IL-12(p40)2 by dendritic cells and subsequent cell migration. J Immunol. 2008;181:5560-7 pubmed..pestis grown at 26 degrees C (Y. pestis-26 degrees), they secrete copious amounts of IL-12p40 homodimer (IL-12(p40)(2)). In contrast, when DCs are exposed to Y. pestis grown at 37 degrees C (Y...
- Lin Y, Ritchea S, Logar A, Slight S, Messmer M, Rangel Moreno J, et al. Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity. 2009;31:799-810 pubmed publisher..Together, these findings illustrate a biological function for IL-17A in regulating IL-12-Th1 cell immunity and host responses to an intracellular pathogen. ..
- Herbert D, Orekov T, Roloson A, Ilies M, Perkins C, O BRIEN W, et al. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol. 2010;184:6438-46 pubmed publisher..Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa. ..
- Ko J, Gendron Fitzpatrick A, Splitter G. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. J Immunol. 2002;168:2433-40 pubmed
- Abdi K. IL-12: the role of p40 versus p75. Scand J Immunol. 2002;56:1-11 pubmed..IL)-12p75 is a heterodimeric cytokine composed of the product of two different genes that specify p35 and p40 subunits...
- Buxbaum L, Uzonna J, Goldschmidt M, Scott P. Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent. Eur J Immunol. 2002;32:3206-15 pubmed..These data uncover the existence of an alternate IFN-gamma and iNOS pathway for control of Leishmania lesions, which is IL-12 independent, but which unexpectedly requires STAT4. ..
- Bastos K, Alvarez J, Marinho C, Rizzo L, Lima M. Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile. J Leukoc Biol. 2002;71:271-8 pubmed..These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites. ..
- Pesce J, Kaviratne M, Ramalingam T, Thompson R, Urban J, Cheever A, et al. The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest. 2006;116:2044-55 pubmed..Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases. ..
- Fortier A, Doiron K, Saleh M, Grinstein S, Gros P. Restriction of Legionella pneumophila replication in macrophages requires concerted action of the transcriptional regulators Irf1 and Irf8 and nod-like receptors Naip5 and Nlrc4. Infect Immun. 2009;77:4794-805 pubmed publisher..They also suggest that flagellin sensing by the NLR proteins Naip5 and Nlrc4 may be coupled to Irf1-Irf8-mediated transcriptional activation of key effector genes essential for macrophage resistance to L. pneumophila infection. ..
- Demangel C, Bertolino P, Britton W. Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur J Immunol. 2002;32:994-1002 pubmed
- Becher B, Durell B, Noelle R. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest. 2002;110:493-7 pubmed..IL-12 is a heterodimer composed of a p35 subunit and a common p40 subunit shared by other cytokines. Both IL-12 p40(-/-) and p35(-/-) mice fail to produce IL-12 p70 heterodimer...
- Jankovic D, Kullberg M, Hieny S, Caspar P, Collazo C, Sher A. In the absence of IL-12, CD4(+) T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10(-/-) setting. Immunity. 2002;16:429-39 pubmed
- Wang S, Bao Y, Rosenberger C, Tesfaigzi Y, Stark J, Harrod K. IL-12p40 and IL-18 modulate inflammatory and immune responses to respiratory syncytial virus infection. J Immunol. 2004;173:4040-9 pubmed..These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance. ..
- Khader S, Pearl J, Sakamoto K, Gilmartin L, Bell G, Jelley Gibbs D, et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175:788-95 pubmed
- Teng M, Andrews D, McLaughlin N, von Scheidt B, Ngiow S, Möller A, et al. IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis. Proc Natl Acad Sci U S A. 2010;107:8328-33 pubmed publisher..Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A. ..
- Leemans J, Wieland C, Florquin S, van der Poll T, Vervoordeldonk M. Mice overexpressing p40 in lungs have reduced leucocyte influx and slightly impaired resistance during tuberculosis. Immunology. 2006;117:409-18 pubmedInterleukin (IL)-12 (p70) is a heterodimeric cytokine composed of p40 and p35, that plays a major role in the protective immune response to Mycobacterium tuberculosis. To define the role of p40 in lungs during pulmonary M...
- Murray H, Tsai C, Liu J, Ma X. Responses to Leishmania donovani in mice deficient in interleukin-12 (IL-12), IL-12/IL-23, or IL-18. Infect Immun. 2006;74:4370-4 pubmed..Nevertheless, testing in IL-18(-/-) mice compared to wild-type mice and in IL-12p40(-/-) compared to IL-12p35(-/-) mice also suggested both early-acting (IL-18) and late-acting (IL-23) antileishmanial effects independent of IL-12. ..
- Becker C, Dornhoff H, Neufert C, Fantini M, Wirtz S, Huebner S, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol. 2006;177:2760-4 pubmedAlthough IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease...
- Amprey J, Im J, Turco S, Murray H, Illarionov P, Besra G, et al. A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. J Exp Med. 2004;200:895-904 pubmed..Together, these data identify Leishmania surface glycoconjugates as potential glycolipid antigens and suggest an important role for the CD1d-NK T cell immune axis in the early response to visceral Leishmania infection. ..
- Tyznik A, Tupin E, Nagarajan N, Her M, Benedict C, Kronenberg M. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J Immunol. 2008;181:4452-6 pubmed..Consequently, iNKT cells have the ability to respond to a variety of microbes, including viruses, in an Ag-independent manner, suggesting they may play a broad role in antipathogen defenses despite their limited TCR repertoire. ..
- Onari Y, Yokoyama A, Haruta Y, Nakashima T, Iwamoto H, Hattori N, et al. IL-12p40 is essential for the down-regulation of airway hyperresponsiveness in a mouse model of bronchial asthma with prolonged antigen exposure. Clin Exp Allergy. 2009;39:290-8 pubmed publisher..The results suggest that endogenous IL-12p40 is essential for inhibition of AHR and peribronchial fibrosis, but not eosinophilic inflammation, in a murine asthma model with prolonged antigen exposures. ..
- Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640-3 pubmed..These findings demonstrate that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense. ..
- Bombeiro A, D Império Lima M, Chadi G, Alvarez J. Neurodegeneration and increased production of nitrotyrosine, nitric oxide synthase, IFN-gamma and S100beta protein in the spinal cord of IL-12p40-deficient mice infected with Trypanosoma cruzi. Neuroimmunomodulation. 2010;17:67-78 pubmed publisher..In the current work, we studied the expression of NO, interferon (IFN)-gamma and S100beta in the spinal cord tissue of IL-12p40KO mice infected with T. cruzi, a model of neurodegenerative process...
- Kawakami K, Kinjo Y, Yara S, Uezu K, Koguchi Y, Tohyama M, et al. Enhanced gamma interferon production through activation of Valpha14(+) natural killer T cells by alpha-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis. Infect Immun. 2001;69:6643-50 pubmed..Our results indicated that in IL-18KO mice, IFN-gamma synthesis was enhanced through overproduction of IL-12 and IL-4 after intravenous infection with C. neoformans and a ligand-specific activation of Valpha14(+) NKT cells. ..
- Langrish C, Chen Y, Blumenschein W, Mattson J, Basham B, Sedgwick J, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233-40 pubmedInterleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12...
- Schulz S, Kohler G, Schütze N, Knauer J, Straubinger R, Chackerian A, et al. Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J Immunol. 2008;181:7891-901 pubmed..In conclusion, IL-23-dependent IL-22, but not IL-17 production is associated with protection against systemic infection with S. Enteritidis in the absence of IL-12. ..
- Sakamoto H, Zhao L, Jain F, Kradin R. IL-12p40(-/-) mice treated with intratracheal bleomycin exhibit decreased pulmonary inflammation and increased fibrosis. Exp Mol Pathol. 2002;72:1-9 pubmed..We conclude that IL-12 promotes the lymphohistiocytic response to BLM and may inhibit the late development of pulmonary fibrosis. ..
- Huaux F, Arras M, Tomasi D, Barbarin V, Delos M, Coutelier J, et al. A profibrotic function of IL-12p40 in experimental pulmonary fibrosis. J Immunol. 2002;169:2653-61 pubmedThe p40 subunit of IL-12 (IL-12p40), but not the heterodimeric form IL-12p70, is secreted during the development of silica-induced lung fibrosis in C57BL/6 mice...
- Tsujimura H, Tamura T, Gongora C, Aliberti J, Reis E Sousa C, Sher A, et al. ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro. Blood. 2003;101:961-9 pubmed..did not mature in response to activation signals, and failed to express CD8alpha and interleukin 12 (IL-12) p40, a feature consistent with ICSBP(-/-) DCs in vivo...
- Ehl S, Bischoff R, Ostler T, Vallbracht S, Schulte Mönting J, Poltorak A, et al. The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus. Eur J Immunol. 2004;34:1146-53 pubmed..These findings clearly argue against a significant role for TLR4 and define a limited role for IL-12 in primary murine RSV infection. ..
- Gutierrez J, Valdez S, di Genaro S, Gomez N. Interleukin-12p40 contributes to protection against lung injury after oral Yersinia enterocolitica infection. Inflamm Res. 2008;57:504-11 pubmed publisher..These results demonstrate that Y. enterocolitica infection may induce inflammatory response in lung and that IL-12p40 could contribute to protection against lung injury. ..
- Maruyama S, Sumita K, Shen H, Kanoh M, Xu X, Sato M, et al. Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter. J Immunol. 2003;170:997-1001 pubmedIL-12 is a heterodimer composed of p40 and p35 and is a key cytokine that functions to protect the host from viral and microbial infections...
- Galvão Da Silva A, Jacysyn J, De Almeida Abrahamsohn I. Resistant mice lacking interleukin-12 become susceptible to Trypanosoma cruzi infection but fail to mount a T helper type 2 response. Immunology. 2003;108:230-7 pubmed..cruzi (Y strain) infection and the regulation of cytokine responses and nitric oxide production in C57BL/6 IL-12 p40-knockout mice...
- Gramaglia I, Sahlin H, Nolan J, Frangos J, Intaglietta M, van der Heyde H. Cell- rather than antibody-mediated immunity leads to the development of profound thrombocytopenia during experimental Plasmodium berghei malaria. J Immunol. 2005;175:7699-707 pubmed
- 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..This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23...