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Gene Review

IL15  -  interleukin 15

Homo sapiens

Synonyms: IL-15, Interleukin-15, MGC9721
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Disease relevance of IL15


Psychiatry related information on IL15

  • The evidence that IL-15 upregulates the expression of coligands that favor the contact between T cells and APC, per se, triggers T-cell activation and proliferation and acts as a chemoattractant for T cells, suggests that IL-15 plays a key role in Tc1-mediated defense mechanisms taking place in extravascular tissues of patients with HIV disease [7].
  • It is proposed that this codependence between IL-12 and IL-15 for the activation of inflammatory T cells may be involved in chronic inflammatory disorders that are dominated by a Th1 response [8].
  • Our findings suggest that interleukin-15 may be implicated in the pathophysiology of Alzheimer's disease and frontotemporal dementia [9].
  • Our results demonstrate that undifferentiated HM were highly resistant to HHV-6 infection, whereas HM pretreated with human recombinant IL-15 showed an increased permissiveness for HHV-6 infection [10].

High impact information on IL15

  • Furthermore, following IM, expression of the receptor for the homeostatic cytokine IL-15 on NK and T cells is lost within these individuals [11].
  • IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis [12].
  • IL-2 is necessary to destroy self-reactive lymphocytes and thus favors peripheral tolerance to self-antigens, whereas IL-15 favors the persistence of lymphocytes involved in the memory and effector responses to invading pathogens but risks the development of inflammatory autoimmune diseases [13].
  • The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens [3].
  • 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 [3].

Chemical compound and disease context of IL15


Biological context of IL15


Anatomical context of IL15

  • These findings may not only explain previous reports of transformation of CTL into NK-like "lymphokine-activated killers" (LAK cells) under high doses of IL2 (a substitute for IL15) but may also have significant implications for understanding and treating immunopathological diseases [23].
  • In a phase I-II clinical trial, HuMax-IL15 was well tolerated clinically, with no significant effects on T lymphocyte subset and natural killer cell numbers [24].
  • Furthermore, we show that TEC-derived soluble factors inhibit generation of NK-CFU and inhibit IL15- or IL2-driven NK cell differentiation from thymic CD34(+) triple-negative thymocytes [25].
  • METHODS: Mononuclear cells from blood and synovial fluid (SF) of RA patients were isolated and cultured in vitro under experimental conditions involving the addition of HuMax-IL15 [24].
  • The increase in IL15 correlated with the increase in TNFalpha (r(s)=0.66, p<0.01); however it did not correlate with the levels of erythrocyte sedimentation rate and C reactive protein, suggesting that IL15 may not be a useful marker in estimating the severity of inflammation in KD [26].

Associations of IL15 with chemical compounds


Physical interactions of IL15


Regulatory relationships of IL15


Other interactions of IL15


Analytical, diagnostic and therapeutic context of IL15


  1. Immune response against human primary malignant melanoma: a distinct cytokine mRNA profile associated with spontaneous regression. Wagner, S.N., Schultewolter, T., Wagner, C., Briedigkeit, L., Becker, J.C., Kwasnicka, H.M., Goos, M. Lab. Invest. (1998) [Pubmed]
  2. Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: influence of recombinant IL12 and IL15. Wagner, H.J., Sili, U., Gahn, B., Vigouroux, S., Huls, M.H., Xie, W., Vignali, D., Brenner, M.K., Heslop, H.E., Rooney, C.M. Cytotherapy. (2003) [Pubmed]
  3. 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]
  4. Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells. Döbbeling, U., Dummer, R., Laine, E., Potoczna, N., Qin, J.Z., Burg, G. Blood (1998) [Pubmed]
  5. Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency. Gilmour, K.C., Fujii, H., Cranston, T., Davies, E.G., Kinnon, C., Gaspar, H.B. Blood (2001) [Pubmed]
  6. Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV. Allison, R.D., Katsounas, A., Koziol, D.E., Kleiner, D.E., Alter, H.J., Lempicki, R.A., Wood, B., Yang, J., Fullmer, B., Cortez, K.J., Polis, M.A., Kottilil, S. J. Infect. Dis. (2009) [Pubmed]
  7. CD8 T-cell infiltration in extravascular tissues of patients with human immunodeficiency virus infection. Interleukin-15 upmodulates costimulatory pathways involved in the antigen-presenting cells-T-cell interaction. Agostini, C., Zambello, R., Facco, M., Perin, A., Piazza, F., Siviero, M., Basso, U., Bortolin, M., Trentin, L., Semenzato, G. Blood (1999) [Pubmed]
  8. IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the absence of TCR ligation. Avice, M.N., Demeure, C.E., Delespesse, G., Rubio, M., Armant, M., Sarfati, M. J. Immunol. (1998) [Pubmed]
  9. IL-15 is elevated in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. Rentzos, M., Zoga, M., Paraskevas, G.P., Kapaki, E., Rombos, A., Nikolaou, C., Tsoutsou, A., Vassilopoulos, D. Journal of geriatric psychiatry and neurology. (2006) [Pubmed]
  10. Role of IL-15 on monocytic resistance to human herpesvirus 6 infection. Arena, A., Merendino, R.A., Bonina, L., Iannello, D., Stassi, G., Mastroeni, P. New Microbiol. (2000) [Pubmed]
  11. Cellular responses to viral infection in humans: lessons from epstein-barr virus. Hislop, A.D., Taylor, G.S., Sauce, D., Rickinson, A.B. Annu. Rev. Immunol. (2007) [Pubmed]
  12. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Ma, A., Koka, R., Burkett, P. Annu. Rev. Immunol. (2006) [Pubmed]
  13. The meandering 45-year odyssey of a clinical immunologist. Waldmann, T.A. Annu. Rev. Immunol. (2003) [Pubmed]
  14. Interleukin-15, a T-cell growth factor, is expressed in human neural cell lines and tissues. Satoh, J., Kurohara, K., Yukitake, M., Kuroda, Y. J. Neurol. Sci. (1998) [Pubmed]
  15. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. Ziolkowska, M., Koc, A., Luszczykiewicz, G., Ksiezopolska-Pietrzak, K., Klimczak, E., Chwalinska-Sadowska, H., Maslinski, W. J. Immunol. (2000) [Pubmed]
  16. Histological characteristics and altered expression of interleukins (IL) IL-13 and IL-15 in endometria of levonorgestrel users with different uterine bleeding patterns. Rhoton-Vlasak, A., Chegini, N., Hardt, N., Williams, R.S. Fertil. Steril. (2005) [Pubmed]
  17. Mucosal Inflammation in Celiac Disease: Interleukin-15 Meets Transforming Growth Factor beta-1. Kagnoff, M.F. Gastroenterology (2007) [Pubmed]
  18. Beneficial effect of short-term exposure of human NK cells to IL15/IL12 and IL15/IL18 on cell apoptosis and function. Sotiriadou, N.N., Perez, S.A., Gritzapis, A.D., Mahaira, L.G., Salagianni, M., Baxevanis, C.N., Papamichail, M. Cell. Immunol. (2005) [Pubmed]
  19. Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides. Tagaya, Y., Kurys, G., Thies, T.A., Losi, J.M., Azimi, N., Hanover, J.A., Bamford, R.N., Waldmann, T.A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes. Zambello, R., Facco, M., Trentin, L., Sancetta, R., Tassinari, C., Perin, A., Milani, A., Pizzolo, G., Rodeghiero, F., Agostini, C., Meazza, R., Ferrini, S., Semenzato, G. Blood (1997) [Pubmed]
  21. Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells. Qin, J.Z., Zhang, C.L., Kamarashev, J., Dummer, R., Burg, G., Döbbeling, U. Blood (2001) [Pubmed]
  22. Decreased interleukin-15 from activated cord versus adult peripheral blood mononuclear cells and the effect of interleukin-15 in upregulating antitumor immune activity and cytokine production in cord blood. Qian, J.X., Lee, S.M., Suen, Y., Knoppel, E., van de Ven, C., Cairo, M.S. Blood (1997) [Pubmed]
  23. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Meresse, B., Chen, Z., Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T.N., Raulet, D.H., Lanier, L.L., Groh, V., Spies, T., Ebert, E.C., Green, P.H., Jabri, B. Immunity (2004) [Pubmed]
  24. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Baslund, B., Tvede, N., Danneskiold-Samsoe, B., Larsson, P., Panayi, G., Petersen, J., Petersen, L.J., Beurskens, F.J., Schuurman, J., van de Winkel, J.G., Parren, P.W., Gracie, J.A., Jongbloed, S., Liew, F.Y., McInnes, I.B. Arthritis Rheum. (2005) [Pubmed]
  25. Human thymic epithelial cells inhibit IL-15- and IL-2-driven differentiation of NK cells from the early human thymic progenitors. Le, P.T., Adams, K.L., Zaya, N., Mathews, H.L., Storkus, W.J., Ellis, T.M. J. Immunol. (2001) [Pubmed]
  26. Raised serum interleukin 15 levels in Kawasaki disease. Jang, G.C., Kim, H.Y., Ahn, S.Y., Kim, D.S. Ann. Rheum. Dis. (2003) [Pubmed]
  27. Interleukin-15 promotes the growth of leukemic cells of patients with B-cell chronic lymphoproliferative disorders. Trentin, L., Cerutti, A., Zambello, R., Sancretta, R., Tassinari, C., Facco, M., Adami, F., Rodeghiero, F., Agostini, C., Semenzato, G. Blood (1996) [Pubmed]
  28. Differential STAT3, STAT5, and NF-kappaB activation in human hematopoietic progenitors by endogenous interleukin-15: implications in the expression of functional molecules. Giron-Michel, J., Caignard, A., Fogli, M., Brouty-Boyé, D., Briard, D., van Dijk, M., Meazza, R., Ferrini, S., Lebousse-Kerdilès, C., Clay, D., Bompais, H., Chouaib, S., Péault, B., Azzarone, B. Blood (2003) [Pubmed]
  29. Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain. Stevens, A.C., Matthews, J., Andres, P., Baffis, V., Zheng, X.X., Chae, D.W., Smith, J., Strom, T.B., Maslinski, W. Am. J. Physiol. (1997) [Pubmed]
  30. Interleukin-15 gene expression in human astrocytes and microglia in culture. Lee, Y.B., Satoh, J., Walker, D.G., Kim, S.U. Neuroreport (1996) [Pubmed]
  31. A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity. Giustiniani, J., Marie-Cardine, A., Bensussan, A. J. Immunol. (2007) [Pubmed]
  32. Immunostimulation by induced expression of NKG2D and its MIC ligands in HTLV-1-associated neurologic disease. Azimi, N., Jacobson, S., Tanaka, Y., Corey, L., Groh, V., Spies, T. Immunogenetics (2006) [Pubmed]
  33. Interleukin 15 induces the signals of epidermal proliferation through ERK and PI 3-kinase in a human epidermal keratinocyte cell line, HaCaT. Yano, S., Komine, M., Fujimoto, M., Okochi, H., Tamaki, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  34. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. McInnes, I.B., Leung, B.P., Sturrock, R.D., Field, M., Liew, F.Y. Nat. Med. (1997) [Pubmed]
  35. 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]
  36. Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells. Kumaki, S., Armitage, R., Ahdieh, M., Park, L., Cosman, D. Eur. J. Immunol. (1996) [Pubmed]
  37. Interleukin-15 differentially enhances the expression of interferon-gamma and interleukin-4 in activated human (CD4+) T lymphocytes. Borger, P., Kauffman, H.F., Postma, D.S., Esselink, M.T., Vellenga, E. Immunology (1999) [Pubmed]
  38. Role of interleukin-15 and interleukin-18 in the secretion of sIL-6R and sgp130 by human neutrophils. Jablonska, E., Marcinczyk, M. Mediators of inflammation. (2003) [Pubmed]
  39. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. McInnes, I.B., al-Mughales, J., Field, M., Leung, B.P., Huang, F.P., Dixon, R., Sturrock, R.D., Wilkinson, P.C., Liew, F.Y. Nat. Med. (1996) [Pubmed]
  40. Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15. Johnston, J.A., Bacon, C.M., Finbloom, D.S., Rees, R.C., Kaplan, D., Shibuya, K., Ortaldo, J.R., Gupta, S., Chen, Y.Q., Giri, J.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  41. Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells. Qin, J.Z., Dummer, R., Burg, G., Döbbeling, U. Blood (1999) [Pubmed]
  42. Interleukin 15 is a potent stimulant of intraepithelial lymphocytes. Ebert, E.C. Gastroenterology (1998) [Pubmed]
  43. Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes. Badolato, R., Ponzi, A.N., Millesimo, M., Notarangelo, L.D., Musso, T. Blood (1997) [Pubmed]
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