IL12A explained

Interleukin-12 subunit alpha (IL-12 p35) is a protein that in humans is encoded by the IL12A gene.^[1]

Function

This gene encodes a subunit of the cytokine Interleukin 12 (IL-12) that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-dependent induction of interferon gamma (IFN-γ), and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity.^[2]

Further reading

• Airoldi I, Guglielmino R, Carra G, Corcione A, Gerosa F, Taborelli G, Trinchieri G, Pistoia V . The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes. . Haematologica . 87 . 4 . 434–42 . 2002 . 11940489 .
• Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB . HIV-1 Vpr and anti-inflammatory activity. . DNA Cell Biol. . 23 . 4 . 239–47 . 2004 . 15142381 . 10.1089/104454904773819824 .
• Zhao RY, Elder RT . Viral infections and cell cycle G2/M regulation. . Cell Res. . 15 . 3 . 143–9 . 2005 . 15780175 . 10.1038/sj.cr.7290279 . free .
• Zhao RY, Bukrinsky M, Elder RT . HIV-1 viral protein R (Vpr) & host cellular responses. . Indian J. Med. Res. . 121 . 4 . 270–86 . 2005 . 15817944 .
• Peluso I, Pallone F, Monteleone G . Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance and therapeutic implication. . World J. Gastroenterol. . 12 . 35 . 5606–10 . 2006 . 17007011 . 10.3748/wjg.v12.i35.5606. 4088159 . free .
• Quaranta MG, Mattioli B, Giordani L, Viora M . The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS. . FASEB J. . 20 . 13 . 2198–208 . 2006 . 17077296 . 10.1096/fj.06-6260rev . free . 3111709 .
• Small RD . Letter: Statistical analysis of respiratory sensitivity to CO₂. . N. Engl. J. Med. . 295 . 7 . 397 . 1976 . 934235 . 10.1056/NEJM197608122950720 .
• Schoenhaut DS, Chua AO, Wolitzky AG, Quinn PM, Dwyer CM, McComas W, Familletti PC, Gately MK, Gubler U . Cloning and expression of murine IL-12. . J. Immunol. . 148 . 11 . 3433–40 . 1992 . 10.4049/jimmunol.148.11.3433 . 1350290 . 44668114 .
• Sieburth D, Jabs EW, Warrington JA, Li X, Lasota J, LaForgia S, Kelleher K, Huebner K, Wasmuth JJ, Wolf SF . Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. . Genomics . 14 . 1 . 59–62 . 1992 . 1358798 . 10.1016/S0888-7543(05)80283-6 .
• Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC . Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. . Proc. Natl. Acad. Sci. U.S.A. . 88 . 10 . 4143–7 . 1991 . 1674604 . 51614 . 10.1073/pnas.88.10.4143 . 1991PNAS...88.4143G . free .
• Kubin M, Kamoun M, Trinchieri G . Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. . J. Exp. Med. . 180 . 1 . 211–22 . 1994 . 7516408 . 2191554 . 10.1084/jem.180.1.211 .
• Ling P, Gately MK, Gubler U, Stern AS, Lin P, Hollfelder K, Su C, Pan YC, Hakimi J . Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity. . J. Immunol. . 154 . 1 . 116–27 . 1995 . 10.4049/jimmunol.154.1.116 . 7527811 . 31733259 . free .
• Sharma V, Knobloch TJ, Benjamin D . Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. . Biochem. Biophys. Res. Commun. . 208 . 2 . 704–13 . 1995 . 7695626 . 10.1006/bbrc.1995.1395 .
• Radrizzani M, Accornero P, Amidei A, Aiello A, Delia D, Kurrle R, Colombo MP . IL-12 inhibits apoptosis induced in a human Th1 clone by gp120/CD4 cross-linking and CD3/TCR activation or by IL-2 deprivation. . Cell. Immunol. . 161 . 1 . 14–21 . 1995 . 7867080 . 10.1006/cimm.1995.1003 .
• Fantuzzi L, Gessani S, Borghi P, Varano B, Conti L, Puddu P, Belardelli F . Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: requirement of gamma interferon for IL-12 secretion. . J. Virol. . 70 . 6 . 4121–4 . 1996 . 8648753 . 190299 . 10.1128/JVI.70.6.4121-4124.1996.
• Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DA, Doherty PC, Grosveld GC, Ihle JN . Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. . Nature . 382 . 6587 . 171–4 . 1996 . 8700208 . 10.1038/382171a0 . 1996Natur.382..171T . 4315628 .
• Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G . Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. . J. Exp. Med. . 184 . 2 . 747–52 . 1996 . 8760829 . 2192696 . 10.1084/jem.184.2.747 .
• Taoufik Y, Lantz O, Wallon C, Charles A, Dussaix E, Delfraissy JF . Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect. . Blood . 89 . 8 . 2842–8 . 1997 . 9108403 . 10.1182/blood.V89.8.2842. free .
• Kim JH, Loveland JE, Sitz KV, Ratto Kim S, Mclinden RJ, Tencer K, Davis K, Burke DS, Boswell RN, Redfield RR, Birx DL . Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1. . Clin. Exp. Immunol. . 108 . 2 . 243–50 . 1997 . 9158092 . 1904649 . 10.1046/j.1365-2249.1997.d01-1006.x .

Notes and References

1. Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM . Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells . J Immunol . 146 . 9 . 3074–81 . May 1991 . 10.4049/jimmunol.146.9.3074 . 1673147 . 23838991 . free .
2. Web site: Entrez Gene: IL12A interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35).