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IL2RA  -  interleukin 2 receptor, alpha

Homo sapiens

 
 
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Disease relevance of IL2RA

  • As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex [1].
  • Unexpectedly, with the appropriate activation of the normal B cells by anti-mu antibody, phorbol myristate acetate, or Staphylococcus aureus Cowan I (SAC), Tac antigen was induced on the activated B cells [2].
  • These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells [3].
  • Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells [3].
  • Northern analysis using a 32P-labeled cDNA probe for the IL 2R p55 protein demonstrated that blood T cells of patients with active sarcoidosis, but not of normal patients, express 3.5- and 1.5-kb IL 2R mRNA transcripts, the same as those observed in normal T cells activated in vitro [4].
 

Psychiatry related information on IL2RA

  • In the 2 CD25 (Tac)- B-NHL patients serum Id levels were below the detection limit and the amount of Id+ Ig secreted in vitro did not surpass 50 ng/ml [5].
  • After a night of sleep deprivation between 10 P.M. and 3 A.M., a reduction of natural immune responses as measured by NK cell activity, NK activity per number of NK cells, LAK activity, and LAK activity per number of LAK precursors (CD16,56, CD25) was found [6].
  • High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder [7].
  • We have previously demonstrated that soluble amyloid beta protein (A beta) induces IL-2 receptor expression and proliferation in peripheral T cells from young and old healthy individuals, but not from patients with Alzheimer's disease (AD) [8].
  • Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R did not differ significantly between nocturnal sleep and nocturnal wakefulness [9].
 

High impact information on IL2RA

  • Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance [10].
  • Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit [11].
  • Both the interleukin-2 receptor-alpha (Tac, p55, IL-2R alpha) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens [12].
  • 5' deletion constructs extending to -327 directed CAT expression in HTLV-I-infected T cells, which express IL2R alpha constitutively, and in Jurkat cells, which express IL2R alpha only after induction [13].
  • We have characterized regulatory regions of the human IL-2 receptor alpha chain (IL2R alpha) promoter [13].
 

Chemical compound and disease context of IL2RA

 

Biological context of IL2RA

 

Anatomical context of IL2RA

  • In further support of the biological significance of these DNA-protein interactions, the IL2RA oligonucleotide from -291 to -245 proved to be sufficient in either orientation to confer PMA inducibility to the mitogen-insensitive thymidine kinase gene promoter in Jurkat cells [19].
  • A novel glycoprotein (IL-2R beta), identified on several lymphocytoid cell lines, has the ability to bind IL-2 alone and to associate with Tac antigen (IL-2R alpha) to form high-affinity IL-2 receptors [23].
  • The expression of the murine interleukin (IL)-2 receptor alpha chain/CD25 is strongly induced at the transcriptional level after T cell activation [24].
  • Detection and functional studies of p60-65 (Tac antigen) on activated human B cells [25].
  • We investigated the effect of OKT3 antibody and interleukin 2 (IL-2) on Tac antigen expression and the proliferation of human peripheral blood mononuclear leukocytes [26].
 

Associations of IL2RA with chemical compounds

  • Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression [27].
  • No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor [3].
  • Tac antigen, the receptor for human interleukin 2 (IL-2), contains in its intracytoplasmic region a serine residue (Ser-247) that is seemingly the predominant site of protein kinase C-mediated phosphorylation [28].
  • After 20 hr of culture, IL-2R mRNA was markedly decreased in both IL-2-toxin- and cycloheximide-treated phytohemagglutinin-activated T cells [29].
  • Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone [30].
 

Physical interactions of IL2RA

  • To distinguish the affinity conversion model and the binary complex model we have carried out kinetic studies on the IL-2 binding to the high affinity IL-2-R on T lymphocytes expressing various numbers of L chains and a relatively constant number of H chains [31].
  • Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both [32].
 

Regulatory relationships of IL2RA

  • Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes [26].
  • IL-15 induced a significant T-cell proliferation and upregulated CD25 expression [33].
  • Culture of human peripheral blood monocytes in vitro induces low level surface expression of the p55 protein of the IL-2R and the expression of this receptor can be enhanced significantly by exposure to IFN-gamma [34].
  • This proliferative effect of TNF was inhibited by an anti-interleukin 2 receptor (IL2R) antibody, MAR 108, which blocks IL2 binding to its receptor [35].
  • Such a small population of CD45RA+ CD4+ T cells expressing CD25 appeared to be present in the blood throughout human life [36].
  • IL2RA has sense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding or non-coding RNAs with antisense Alu elements [37].
 

Other interactions of IL2RA

 

Analytical, diagnostic and therapeutic context of IL2RA

  • CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls [43].
  • Consistent with this, using flow cytometry and an MAb directed against the IL 2R p55 protein (2A3), we observed detectable levels of IL 2R surface protein on increased numbers of blood T cells of active sarcoidosis patients (4.7 +/- 0.9%) compared with blood T cells of normal patients (0.9 +/- 0.2%) [4].
  • Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA [44].
  • Consistent with these findings in cell culture, immunohistologic studies demonstrated p55 and p70 antigen in the vasculature of rheumatoid joints, but not in normal joint tissue [45].
  • Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2-receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats [46].

References

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  2. Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function. Muraguchi, A., Kehrl, J.H., Longo, D.L., Volkman, D.J., Smith, K.A., Fauci, A.S. J. Exp. Med. (1985) [Pubmed]
  3. Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. Uchiyama, T., Hori, T., Tsudo, M., Wano, Y., Umadome, H., Tamori, S., Yodoi, J., Maeda, M., Sawami, H., Uchino, H. J. Clin. Invest. (1985) [Pubmed]
  4. Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis. Konishi, K., Moller, D.R., Saltini, C., Kirby, M., Crystal, R.G. J. Clin. Invest. (1988) [Pubmed]
  5. Idiotypic immunoglobulin secretion by human B cell non-Hodgkin's lymphomas is related to the expression of the interleukin-2 receptor. Vyth-Dreese, F.A., Dellemijn, T.A., Hekman, A., Melief, C.J. Leukemia (1988) [Pubmed]
  6. Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. Irwin, M., McClintick, J., Costlow, C., Fortner, M., White, J., Gillin, J.C. FASEB J. (1996) [Pubmed]
  7. High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder. Breunis, M.N., Kupka, R.W., Nolen, W.A., Suppes, T., Denicoff, K.D., Leverich, G.S., Post, R.M., Drexhage, H.A. Biol. Psychiatry (2003) [Pubmed]
  8. Interactions of the Alzheimer beta amyloid fragment (25-35) with peripheral blood dendritic cells. Schmitt, T.L., Steger, M.M., Pavelka, M., Grubeck-Loebenstein, B. Mech. Ageing Dev. (1997) [Pubmed]
  9. Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers. Haack, M., Pollmächer, T., Mullington, J.M. Brain Behav. Immun. (2004) [Pubmed]
  10. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Sakaguchi, S. Annu. Rev. Immunol. (2004) [Pubmed]
  11. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Waldmann, T.A., Tagaya, Y. Annu. Rev. Immunol. (1999) [Pubmed]
  12. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Böhnlein, E., Lowenthal, J.W., Siekevitz, M., Ballard, D.W., Franza, B.R., Greene, W.C. Cell (1988) [Pubmed]
  13. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cross, S.L., Feinberg, M.B., Wolf, J.B., Holbrook, N.J., Wong-Staal, F., Leonard, W.J. Cell (1987) [Pubmed]
  14. Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. Tsang, K.Y., Fudenberg, H.H., Galbraith, G.M., Donnelly, R.P., Bishop, L.R., Koopmann, W.R. J. Clin. Invest. (1985) [Pubmed]
  15. Inhibition of lymphocyte activation and function by the prenylation inhibitor L-778,123. Si, M.S., Reitz, B.A., Borie, D.C. Investigational new drugs. (2005) [Pubmed]
  16. Immunophenotypic profile of peripheral blood eosinophils in acute graft-vs.-host disease. Rumi, C., Rutella, S., Bonini, S., Bonini, S., Lambiase, A., Sica, S., Puggioni, P., Salutari, P., Etuk, B., Leone, G. Exp. Hematol. (1998) [Pubmed]
  17. High-affinity interleukin 2 receptors on B cell chronic lymphocytic leukemia cells are induced by phorbol myristate acetate but not by calcium ionophore. Mitsui, H., Yagura, H., Tamaki, T., Ikeda, H., Matsumura, I., Kanakura, Y., Yonezawa, T., Tarui, S., Ideka, H. Immunol. Lett. (1991) [Pubmed]
  18. Inhibition of proliferation and CD25 down-regulation by retinoic acid in human adult T cell leukemia cells. Miyatake, J.I., Maeda, Y. Leukemia (1997) [Pubmed]
  19. Regulation of interleukin 2 receptor alpha subunit (Tac or CD25 antigen) gene expression: binding of inducible nuclear proteins to discrete promoter sequences correlates with transcriptional activation. Lowenthal, J.W., Böhnlein, E., Ballard, D.W., Greene, W.C. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  20. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. Anderson, D.M., Kumaki, S., Ahdieh, M., Bertles, J., Tometsko, M., Loomis, A., Giri, J., Copeland, N.G., Gilbert, D.J., Jenkins, N.A. J. Biol. Chem. (1995) [Pubmed]
  21. Human chromosome 10 loci map to three different sheep chromosomes. Ansari, H.A., Pearce, P.D., Maher, D.W., Broad, T.E. Mamm. Genome (1995) [Pubmed]
  22. Shared synteny between human chromosome 10 and chromosome 1 of the marsupial tammar wallaby, Macropus eugenii. Spurdle, A.B., Maccarone, P., Toder, R., Wilcox, S.A., Graves, J.A. Cytogenet. Cell Genet. (1997) [Pubmed]
  23. The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Siegel, J.P., Sharon, M., Smith, P.L., Leonard, W.J. Science (1987) [Pubmed]
  24. The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells. Schuh, K., Twardzik, T., Kneitz, B., Heyer, J., Schimpl, A., Serfling, E. J. Exp. Med. (1998) [Pubmed]
  25. Detection and functional studies of p60-65 (Tac antigen) on activated human B cells. Jung, L.K., Hara, T., Fu, S.M. J. Exp. Med. (1984) [Pubmed]
  26. Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes. Welte, K., Andreeff, M., Platzer, E., Holloway, K., Rubin, B.Y., Moore, M.A., Mertelsmann, R. J. Exp. Med. (1984) [Pubmed]
  27. Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class II major histocompatibility complex-restricted antigen-specific T helper clones. T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals. Oyaizu, N., Chirmule, N., Pahwa, S. J. Clin. Invest. (1992) [Pubmed]
  28. Intracytoplasmic phosphorylation sites of Tac antigen (p55) are not essential for the conformation, function, and regulation of the human interleukin 2 receptor. Hatakeyama, M., Minamoto, S., Taniguchi, T. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  29. Sequential effects of interleukin 2-diphtheria toxin fusion protein on T-cell activation. Walz, G., Zanker, B., Brand, K., Waters, C., Genbauffe, F., Zeldis, J.B., Murphy, J.R., Strom, T.B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  30. Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids. Mori, A., Kaminuma, O., Suko, M., Inoue, S., Ohmura, T., Hoshino, A., Asakura, Y., Miyazawa, K., Yokota, T., Okumura, Y., Ito, K., Okudaira, H. Blood (1997) [Pubmed]
  31. A larger number of L chains (Tac) enhance the association rate of interleukin 2 to the high affinity site of the interleukin 2 receptor. Saito, Y., Sabe, H., Suzuki, N., Kondo, S., Ogura, T., Shimizu, A., Honjo, T. J. Exp. Med. (1988) [Pubmed]
  32. Interleukin-12 activates human gamma delta T cells: synergistic effect of tumor necrosis factor-alpha. Ueta, C., Kawasumi, H., Fujiwara, H., Miyagawa, T., Kida, H., Ohmoto, Y., Kishimoto, S., Tsuyuguchi, I. Eur. J. Immunol. (1996) [Pubmed]
  33. The role of interleukin-10 (IL-10) in IL-15-mediated T-cell responses. Körholz, D., Banning, U., Bönig, H., Grewe, M., Schneider, M., Mauz-Körholz, C., Klein-Vehne, A., Krutmann, J., Burdach, S. Blood (1997) [Pubmed]
  34. Functional consequences of monocyte IL-2 receptor expression. Induction of IL-1 beta secretion by IFN gamma and IL-2. Herrmann, F., Cannistra, S.A., Lindemann, A., Blohm, D., Rambaldi, A., Mertelsmann, R.H., Griffin, J.D. J. Immunol. (1989) [Pubmed]
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  36. A novel subpopulation of CD45RA+ CD4+ T cells expressing IL-2 receptor alpha-chain (CD25) and having a functionally transitional nature into memory cells. Kanegane, H., Miyawaki, T., Kato, K., Yokoi, T., Uehara, T., Yachie, A., Taniguchi, N. Int. Immunol. (1991) [Pubmed]
  37. A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs. Liang, K.H., Yeh, C.T. BMC. Genomics. (2013) [Pubmed]
  38. A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Dukovich, M., Wano, Y., Le thi Bich Thuy, n.u.l.l., Katz, P., Cullen, B.R., Kehrl, J.H., Greene, W.C. Nature (1987) [Pubmed]
  39. Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex. Tsudo, M., Kozak, R.W., Goldman, C.K., Waldmann, T.A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  40. Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor. Burton, J., Goldman, C.K., Rao, P., Moos, M., Waldmann, T.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
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  43. Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function. Farmer, D.G., McDiarmid, S.V., Edelstein, S., Renz, J.F., Hisatake, G., Cortina, G., Fondevila, C., Correa, M., Rhodes, S., Zafar, A., Chavez, Y., Yersiz, H., Busuttil, R.W. Transplant. Proc. (2004) [Pubmed]
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  45. Interferon-alpha and interleukin 2 synergistically enhance basic fibroblast growth factor synthesis and induce release, promoting endothelial cell growth. Cozzolino, F., Torcia, M., Lucibello, M., Morbidelli, L., Ziche, M., Platt, J., Fabiani, S., Brett, J., Stern, D. J. Clin. Invest. (1993) [Pubmed]
  46. Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes. Signore, A., Parman, A., Pozzilli, P., Andreani, D., Beverley, P.C. Lancet (1987) [Pubmed]
 
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