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Gene Review

Il15  -  interleukin 15

Mus musculus

Synonyms: AI503618, IL-15, Interleukin-15
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Disease relevance of Il15

  • To investigate the role of IL-15 in psoriasis, we generated mAb's using human immunoglobulin-transgenic mice [1].
  • Furthermore, mice with severe combined immunodeficiency treated with the Fab fragment of a blocking antibody recognizing a signaling subunit of the IL-15 receptor, IL-2/15Rbeta, had a significant ( approximately 90%) loss of NK cells compared with control mice [2].
  • Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice [3].
  • IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases [3].
  • RESULTS: IL-15 KO mice exhibited resistance to DSS induced acute colitis, as reflected by lower lethality, weight loss, clinical scores, and histological scores compared with those in control mice (p<0.05) [3].
  • Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis [4].

Psychiatry related information on Il15


High impact information on Il15


Chemical compound and disease context of Il15


Biological context of Il15


Anatomical context of Il15

  • Interleukin (IL)-2 and IL-15 are redundant in stimulating T-cell proliferation in vitro [8].
  • High concentrations of IL-15 blocked TCR alpha beta development and shifted differentiation towards NK cells [17].
  • Data obtained from in situ hybridization study have suggested that the macrophages present in the pregnant uterus may be responsible for the production of IL-15 [21].
  • Here, it is shown that IL-15 mRNA is mainly expressed in thymic epithelial stromal cells, whereas IL-2 mRNA is exclusively expressed in thymocytes [17].
  • Here, we examine the effect of IL-15 on hyaluronan expression by endothelial cells, and investigate its role in vivo in promoting the extravasation of antigen-activated T cells through a CD44-dependent pathway [22].

Associations of Il15 with chemical compounds


Physical interactions of Il15


Regulatory relationships of Il15

  • Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy [30].
  • We have examined the induction of IL-15 in murine macrophages (by semiquantitative reverse transcriptase-PCR and bioassay) in response to a variety of different macrophage-activating stimuli and compared the regulation of IL-15 production to that of IL-12 and TNF-alpha [31].
  • We show here the effects of IL-15 on the proliferation and maintenance of murine gamma delta i-IEL in vitro. gamma delta i-IEL constitutively expressed a high level of IL-15 receptor alpha mRNA and proliferated in response to IL-15 more vigorously than alpha beta i-IEL [32].
  • Consistent with this idea, IL-15 stimulates sustained STAT5 phosphorylation in SOCS1-deficient CD8+ T cells [33].
  • Although effects of IL-15 on Mphi activities have not previously been reported, its derivation from activated Mphi suggested a possible autocrine role in regulating Mphi functions and prompted us to determine whether IL-15 modulated LPS-activated Mphi cytokine production [34].

Other interactions of Il15


Analytical, diagnostic and therapeutic context of Il15


  1. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. Villadsen, L.S., Schuurman, J., Beurskens, F., Dam, T.N., Dagnaes-Hansen, F., Skov, L., Rygaard, J., Voorhorst-Ogink, M.M., Gerritsen, A.F., van Dijk, M.A., Parren, P.W., Baadsgaard, O., van de Winkel, J.G. J. Clin. Invest. (2003) [Pubmed]
  2. In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Cooper, M.A., Bush, J.E., Fehniger, T.A., VanDeusen, J.B., Waite, R.E., Liu, Y., Aguila, H.L., Caligiuri, M.A. Blood (2002) [Pubmed]
  3. Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Yoshihara, K., Yajima, T., Kubo, C., Yoshikai, Y. Gut (2006) [Pubmed]
  4. IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities. Orinska, Z., Maurer, M., Mirghomizadeh, F., Bulanova, E., Metz, M., Nashkevich, N., Schiemann, F., Schulmistrat, J., Budagian, V., Giron-Michel, J., Brandt, E., Paus, R., Bulfone-Paus, S. Nat. Med. (2007) [Pubmed]
  5. Viral activation of interleukin-15 (IL-15): characterization of a virus-inducible element in the IL-15 promoter region. Azimi, N., Shiramizu, K.M., Tagaya, Y., Mariner, J., Waldmann, T.A. J. Virol. (2000) [Pubmed]
  6. Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Teague, R.M., Sather, B.D., Sacks, J.A., Huang, M.Z., Dossett, M.L., Morimoto, J., Tan, X., Sutton, S.E., Cooke, M.P., Ohlén, C., Greenberg, P.D. Nat. Med. (2006) [Pubmed]
  7. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Brentjens, R.J., Latouche, J.B., Santos, E., Marti, F., Gong, M.C., Lyddane, C., King, P.D., Larson, S., Weiss, M., Rivière, I., Sadelain, M. Nat. Med. (2003) [Pubmed]
  8. IL-15 and IL-2: a matter of life and death for T cells in vivo. Li, X.C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T.R., Strom, T.B. Nat. Med. (2001) [Pubmed]
  9. Interleukin-15 protects from lethal apoptosis in vivo. Bulfone-Paus, S., Ungureanu, D., Pohl, T., Lindner, G., Paus, R., Rückert, R., Krause, H., Kunzendorf, U. Nat. Med. (1997) [Pubmed]
  10. The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Atherly, L.O., Lucas, J.A., Felices, M., Yin, C.C., Reiner, S.L., Berg, L.J. Immunity (2006) [Pubmed]
  11. Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. Kimura, Y., Takeshita, T., Kondo, M., Ishii, N., Nakamura, M., Van Snick, J., Sugamura, K. Int. Immunol. (1995) [Pubmed]
  12. Immunoregulation during disease progression in prediabetic NOD mice: inverse expression of arginase and prostaglandin H synthase 2 vs. interleukin-15. Rothe, H., Hausmann, A., Kolb, H. Horm. Metab. Res. (2002) [Pubmed]
  13. Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin infection in IL-15-deficient mice. Saito, K., Yajima, T., Kumabe, S., Doi, T., Yamada, H., Sad, S., Shen, H., Yoshikai, Y. J. Immunol. (2006) [Pubmed]
  14. Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery. Bolesta, E., Kowalczyk, A., Wierzbicki, A., Eppolito, C., Kaneko, Y., Takiguchi, M., Stamatatos, L., Shrikant, P.A., Kozbor, D. J. Immunol. (2006) [Pubmed]
  15. IL-12 or IL-15, unlike IL-2, does not interact with histamine in augmenting cytotoxicity of splenocytes against melanoma cells and YAC-1 cells. Kozar, K., Kaminski, R., Giermasz, A., Basak, G., Zagozdzon, R., Rybczynska, J., Wasik, M., Lasek, W., Jakobisiak, M., Golab, J. Oncol. Rep. (2002) [Pubmed]
  16. Chromosomal assignment and genomic structure of Il15. Anderson, D.M., Johnson, L., Glaccum, M.B., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Valentine, V., Kirstein, M.N., Shapiro, D.N., Morris, S.W. Genomics (1995) [Pubmed]
  17. Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. Leclercq, G., Debacker, V., de Smedt, M., Plum, J. J. Exp. Med. (1996) [Pubmed]
  18. Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. Giri, J.G., Kumaki, S., Ahdieh, M., Friend, D.J., Loomis, A., Shanebeck, K., DuBose, R., Cosman, D., Park, L.S., Anderson, D.M. EMBO J. (1995) [Pubmed]
  19. Identification of a novel receptor/signal transduction pathway for IL-15/T in mast cells. Tagaya, Y., Burton, J.D., Miyamoto, Y., Waldmann, T.A. EMBO J. (1996) [Pubmed]
  20. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Ranson, T., Vosshenrich, C.A., Corcuff, E., Richard, O., Müller, W., Di Santo, J.P. Blood (2003) [Pubmed]
  21. The involvement of interleukin (IL)-15 in regulating the differentiation of granulated metrial gland cells in mouse pregnant uterus. Ye, W., Zheng, L.M., Young, J.D., Liu, C.C. J. Exp. Med. (1996) [Pubmed]
  22. Interleukin 15 induces endothelial hyaluronan expression in vitro and promotes activated T cell extravasation through a CD44-dependent pathway in vivo. Estess, P., Nandi, A., Mohamadzadeh, M., Siegelman, M.H. J. Exp. Med. (1999) [Pubmed]
  23. Suppressor of cytokine signaling 1 stringently regulates distinct functions of IL-7 and IL-15 in vivo during T lymphocyte development and homeostasis. Ramanathan, S., Gagnon, J., Leblanc, C., Rottapel, R., Ilangumaran, S. J. Immunol. (2006) [Pubmed]
  24. Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity. Hanisch, U.K., Lyons, S.A., Prinz, M., Nolte, C., Weber, J.R., Kettenmann, H., Kirchhoff, F. J. Biol. Chem. (1997) [Pubmed]
  25. Blocking IL-15 prevents the induction of allergen-specific T cells and allergic inflammation in vivo. Rückert, R., Brandt, K., Braun, A., Hoymann, H.G., Herz, U., Budagian, V., Dürkop, H., Renz, H., Bulfone-Paus, S. J. Immunol. (2005) [Pubmed]
  26. Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis. Kuniyasu, H., Ohmori, H., Sasaki, T., Sasahira, T., Yoshida, K., Kitadai, Y., Fidler, I.J. Clin. Cancer Res. (2003) [Pubmed]
  27. Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice. Varma, T.K., Toliver-Kinsky, T.E., Lin, C.Y., Koutrouvelis, A.P., Nichols, J.E., Sherwood, E.R. Infect. Immun. (2001) [Pubmed]
  28. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Lodolce, J.P., Boone, D.L., Chai, S., Swain, R.E., Dassopoulos, T., Trettin, S., Ma, A. Immunity (1998) [Pubmed]
  29. The NF-kappaB binding site is essential for transcriptional activation of the IL-15 gene. Washizu, J., Nishimura, H., Nakamura, N., Nimura, Y., Yoshikai, Y. Immunogenetics (1998) [Pubmed]
  30. Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2. Roychowdhury, S., May, K.F., Tzou, K.S., Lin, T., Bhatt, D., Freud, A.G., Guimond, M., Ferketich, A.K., Liu, Y., Caligiuri, M.A. Cancer Res. (2004) [Pubmed]
  31. Induction and regulation of IL-15 expression in murine macrophages. Doherty, T.M., Seder, R.A., Sher, A. J. Immunol. (1996) [Pubmed]
  32. Interleukin-15 preferentially promotes the growth of intestinal intraepithelial lymphocytes bearing gamma delta T cell receptor in mice. Inagaki-Ohara, K., Nishimura, H., Mitani, A., Yoshikai, Y. Eur. J. Immunol. (1997) [Pubmed]
  33. Suppressor of cytokine signaling 1 regulates IL-15 receptor signaling in CD8+CD44high memory T lymphocytes. Ilangumaran, S., Ramanathan, S., La Rose, J., Poussier, P., Rottapel, R. J. Immunol. (2003) [Pubmed]
  34. IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: evidence for differential receptor subunit utilization associated with stimulation or inhibition. Alleva, D.G., Kaser, S.B., Monroy, M.A., Fenton, M.J., Beller, D.I. J. Immunol. (1997) [Pubmed]
  35. Interleukin-15 induces IL-12 receptor beta1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. Musikacharoen, T., Oguma, A., Yoshikai, Y., Chiba, N., Masuda, A., Matsuguchi, T. Blood (2005) [Pubmed]
  36. Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells. Schluns, K.S., Klonowski, K.D., Lefrançois, L. Blood (2004) [Pubmed]
  37. Suppressor of cytokine signaling 1 attenuates IL-15 receptor signaling in CD8+ thymocytes. Ilangumaran, S., Ramanathan, S., Ning, T., La Rose, J., Reinhart, B., Poussier, P., Rottapel, R. Blood (2003) [Pubmed]
  38. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Huntington, N.D., Puthalakath, H., Gunn, P., Naik, E., Michalak, E.M., Smyth, M.J., Tabarias, H., Degli-Esposti, M.A., Dewson, G., Willis, S.N., Motoyama, N., Huang, D.C., Nutt, S.L., Tarlinton, D.M., Strasser, A. Nat. Immunol. (2007) [Pubmed]
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