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Gene Review

Il2ra  -  interleukin 2 receptor, alpha chain

Mus musculus

Synonyms: CD25, IL-2 receptor subunit alpha, IL-2-RA, IL-2R alpha chain, IL-2R subunit alpha, ...
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Disease relevance of Il2ra


High impact information on Il2ra

  • Unlike the IL-2R alpha chain, the IL-2R beta chain contains a large cytoplasmic domain that shows no obvious tyrosine kinase motif [6].
  • The mechanism of induction of CD25 before T cell receptor rearrangement and the importance of this mechanism for T cell development are unknown [7].
  • Functionally distinct NF-kappa B binding sites in the immunoglobulin kappa and IL-2 receptor alpha chain genes [8].
  • We show that expression of Foxp3 is highly restricted to the subset alphabeta of T cells and, irrespective of CD25 expression, correlates with suppressor activity [9].
  • In recombinase gene null pre-T cells, membrane and cytosolic active PKD both induced differentiation reminiscent of beta selection: downregulation of CD25 and upregulation of CD2 and CD5 [10].

Biological context of Il2ra

  • Spleen cells from mice bearing progressive growing methylcholanthrene-induced syngenic tumours were deeply hyporeactive in response to T-cell mitogens. This hyporeactivity was associated with decreased ability to synthesize mRNA for the inducible 55,000 MW interleukin-2 receptor (IL-2R ) [14].
  • The stimulation with Con A of spleen cells from newborn mice, in contrast to cells from adult animals, does not result in synthesis of mRNA for inducible 55,000 molecular weight (MW) IL-2 receptors (IL-2R/CD25). The failure of neonatal spleen cells to synthesize IL-2R mRNA is an intrinsic property of the cells themselves, and it is not due to activity of natural suppressor cells present in newborn animals [15] .


Anatomical context of Il2ra


Associations of Il2ra with chemical compounds

  • We previously reported that IL-7 maintains the viability and differentiation potential of CD25 (IL-2R p55) positive CD3-CD4-CD8- thymic pre-T cells in vitro [20].
  • Tumor necrosis factor and its p55 and p75 receptors are not required for axonal lesion-induced microgliosis in mouse fascia dentata [21].
  • Furthermore, topical FK506 profoundly impaired oxazolone-induced up-regulation of CD25 expression on CD4+ LNC and dramatically decreased hapten-induced expansion of I-A+/B220+ and I-A+/CD69+ LNC subsets [22].
  • IL-2 initially binds a high mannose-type glycan and a specific peptide sequence of the IL-2 receptor alpha-subunit and sequentially forms a high affinity complex of IL-2.IL-2 receptor alpha-, beta-, and gamma-subunits [23].
  • IL-2Ralpha (CD25) expression on activated cells was significantly reduced by epicatechin and cocoa extract in a dose-dependent manner, achieving the highest inhibition of about 50 % when flavonoids were added 2 h before stimulation [24].

Physical interactions of Il2ra

  • Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun [25].

Regulatory relationships of Il2ra


Other interactions of Il2ra

  • Interleukin 2 signaling is believed to be critically involved in several aspects of CD25(+) CD4(+) regulatory T cell biology, such as intrathymic development, peripheral survival and suppressive function [30].
  • 1-2% of adult mouse thymocytes express the T cell receptor alpha/beta (TCR-alpha/beta) together with the interleukin (IL) 2R beta (p70), but not the alpha (p 55) chain [31].
  • In infected mice, two subpopulations of CD4(+) cells, separable by their expression of CD25, make IL-10 [18].
  • Pre-treated CD8 T cells from both age groups also displayed a significant increase in activation-induced CD69 and CD25 expression, and produced significantly higher amounts of interleukin-2 and interferon-gamma in comparison to their untreated counterparts [32].
  • High affinity IL-2R signalling in the context of CD25 and the microdomain environment is characterized by Jak3 activation [27].

Analytical, diagnostic and therapeutic context of Il2ra


  1. IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Wakabayashi, K., Lian, Z.X., Moritoki, Y., Lan, R.Y., Tsuneyama, K., Chuang, Y.H., Yang, G.X., Ridgway, W., Ueno, Y., Ansari, A.A., Coppel, R.L., Mackay, I.R., Gershwin, M.E. Hepatology (2006) [Pubmed]
  2. Functional responses and apoptosis of CD25 (IL-2R alpha)-deficient T cells expressing a transgenic antigen receptor. Van Parijs, L., Biuckians, A., Ibragimov, A., Alt, F.W., Willerford, D.M., Abbas, A.K. J. Immunol. (1997) [Pubmed]
  3. Anti-CD3:anti-IL-2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro. MacLean, J.A., Su, Z., Guo, Y., Sy, M.S., Colvin, R.B., Wong, J.T. J. Immunol. (1993) [Pubmed]
  4. IL-2 receptor alpha chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. Rolink, A., Grawunder, U., Winkler, T.H., Karasuyama, H., Melchers, F. Int. Immunol. (1994) [Pubmed]
  5. Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Papiernik, M., de Moraes, M.L., Pontoux, C., Vasseur, F., Pénit, C. Int. Immunol. (1998) [Pubmed]
  6. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Hatakeyama, M., Mori, H., Doi, T., Taniguchi, T. Cell (1989) [Pubmed]
  7. Requirement for TNF-alpha and IL-1 alpha in fetal thymocyte commitment and differentiation. Zúñiga-Pflücker, J.C., Di, J., Lenardo, M.J. Science (1995) [Pubmed]
  8. Functionally distinct NF-kappa B binding sites in the immunoglobulin kappa and IL-2 receptor alpha chain genes. Cross, S.L., Halden, N.F., Lenardo, M.J., Leonard, W.J. Science (1989) [Pubmed]
  9. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Fontenot, J.D., Rasmussen, J.P., Williams, L.M., Dooley, J.L., Farr, A.G., Rudensky, A.Y. Immunity (2005) [Pubmed]
  10. Intracellular location and cell context-dependent function of protein kinase D. Marklund, U., Lightfoot, K., Cantrell, D. Immunity (2003) [Pubmed]
  11. The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2 response elements. Kim, H.P., Kelly, J., Leonard, W.J. Immunity (2001) [Pubmed]
  12. Murine T-lymphocyte proliferation induced by interleukin 2 correlates with a transient increase in p56lck kinase activity and the tyrosine phosphorylation of a 97-kDa protein. Kim, Y.H., Buchholz, M.J., Nordin, A.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  13. Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. Matsumoto, A., Seki, Y., Kubo, M., Ohtsuka, S., Suzuki, A., Hayashi, I., Tsuji, K., Nakahata, T., Okabe, M., Yamada, S., Yoshimura, A. Mol. Cell. Biol. (1999) [Pubmed]
  14. Tumour-bearing animals synthesize a decreased level of mRNA for the inducible 55,000 MW interleukin-2 receptor. Holán, V., Lipoldová, M. Immunology. (1990) [Pubmed]
  15. Inability of mitogen-stimulated spleen cells from newborn mice to synthesize interleukin-2 receptors. Lipoldová, M., Zajícová, A., Holán, V. Immunology. (1990) [Pubmed]
  16. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Fontenot, J.D., Rasmussen, J.P., Gavin, M.A., Rudensky, A.Y. Nat. Immunol. (2005) [Pubmed]
  17. An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines. Hwang, E.S., White, I.A., Ho, I.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. McKee, A.S., Pearce, E.J. J. Immunol. (2004) [Pubmed]
  19. FTY720 Ameliorates Th1-Mediated Colitis in Mice by Directly Affecting the Functional Activity of CD4+CD25+ Regulatory T Cells. Daniel, C., Sartory, N., Zahn, N., Geisslinger, G., Radeke, H.H., Stein, J.M. J. Immunol. (2007) [Pubmed]
  20. In vitro induction of CD8 expression on thymic pre-T cells. I. Transforming growth factor-beta and tumor necrosis factor-alpha induce CD8 expression on CD8- thymic subsets including the CD25+CD3-CD4-CD8- pre-T cell subset. Suda, T., Zlotnik, A. J. Immunol. (1992) [Pubmed]
  21. Tumor necrosis factor and its p55 and p75 receptors are not required for axonal lesion-induced microgliosis in mouse fascia dentata. Fenger, C., Drojdahl, N., Wirenfeldt, M., Sylvest, L., Jorgensen, O.S., Meldgaard, M., Lambertsen, K.L., Finsen, B. Glia (2006) [Pubmed]
  22. Topical FK506 suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during primary skin immune responses. Homey, B., Assmann, T., Vohr, H.W., Ulrich, P., Lauerma, A.I., Ruzicka, T., Lehmann, P., Schuppe, H.C. J. Immunol. (1998) [Pubmed]
  23. Carbohydrate recognition site of interleukin-2 in relation to cell proliferation. Fukushima, K., Hara-Kuge, S., Ideo, H., Yamashita, K. J. Biol. Chem. (2001) [Pubmed]
  24. Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line. Ramiro, E., Franch, A., Castellote, C., Andrés-Lacueva, C., Izquierdo-Pulido, M., Castell, M. Br. J. Nutr. (2005) [Pubmed]
  25. STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus. O'Sullivan, A., Chang, H.C., Yu, Q., Kaplan, M.H. J. Biol. Chem. (2004) [Pubmed]
  26. Unexpected effects of the IL-2 receptor alpha subunit on high affinity IL-2 receptor assembly and function detected with a mutant IL-2 analog. Kuziel, W.A., Ju, G., Grdina, T.A., Greene, W.C. J. Immunol. (1993) [Pubmed]
  27. Possible mechanism for the alpha subunit of the interleukin-2 receptor (CD25) to influence interleukin-2 receptor signal transduction. Ellery, J.M., Nicholls, P.J. Immunol. Cell Biol. (2002) [Pubmed]
  28. Second signal activity of IL-12 on the proliferation and IL-2R expression of T helper cell-1 clone. Yanagida, T., Kato, T., Igarashi, O., Inoue, T., Nariuchi, H. J. Immunol. (1994) [Pubmed]
  29. Contrasting effect of transforming growth factor type beta 1 (TGF-beta 1) on proliferation and interleukin-2 receptor expression in activated and rapidly cycling immature (CD3-CD4-CD8-) thymocytes. Dupuy d'Angeac, A., Rème, T., Monier, S., Gao, Q., Duperray, C., Jullien, P., Dornand, J. J. Cell. Physiol. (1993) [Pubmed]
  30. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. D'Cruz, L.M., Klein, L. Nat. Immunol. (2005) [Pubmed]
  31. Induction of interleukin 2 receptor beta chain expression by self-recognition in the thymus. Hanke, T., Mitnacht, R., Boyd, R., Hünig, T. J. Exp. Med. (1994) [Pubmed]
  32. Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice. Sadighi Akha, A.A., Berger, S.B., Miller, R.A. Immunology (2006) [Pubmed]
  33. Incomplete Depletion and Rapid Regeneration of Foxp3+ Regulatory T Cells Following Anti-CD25 Treatment in Malaria-Infected Mice. Couper, K.N., Blount, D.G., de Souza, J.B., Suffia, I., Belkaid, Y., Riley, E.M. J. Immunol. (2007) [Pubmed]
  34. T cell activation in the absence of interleukin 2 (IL 2) results in the induction of high-affinity IL 2 receptor unable to transmit a proliferative signal. Proust, J.J., Shaper, N.L., Buchholz, M.A., Nordin, A.A. Eur. J. Immunol. (1991) [Pubmed]
  35. Dynamics of CD4+CD25+ T Cells in Spleens and Mesenteric Lymph Nodes of Mice Infected with Schistosoma japonicum. Cai, X.P., Zhang, H., Zhang, Y.C., Wang, Y., Su, C., Ji, M.J., Wu, H.W., Zhu, X., Zhang, Z.S., Wu, G.L. Acta Biochim. Biophys. Sin. (Shanghai) (2006) [Pubmed]
  36. Ryanodine receptor signaling is required for anti-CD3-induced T cell proliferation, interleukin-2 synthesis, and interleukin-2 receptor signaling. Conrad, D.M., Hanniman, E.A., Watson, C.L., Mader, J.S., Hoskin, D.W. J. Cell. Biochem. (2004) [Pubmed]
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