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Gene Review

Il13  -  interleukin 13

Mus musculus

Synonyms: IL-13, Il-13, Interleukin-13, T-cell activation protein P600
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Disease relevance of Il13


Psychiatry related information on Il13


High impact information on Il13

  • Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity [9].
  • The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281(-/-) mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d(-/-) mice of recombinant IL-13, which directly affects airway smooth muscle cells [9].
  • T helper 2 (T(H)2) cells elaborate cytokines, such as interleukin (IL)-4, IL-5, IL-9 and IL-13, which work with toxic mediators of innate immune cells to establish environments that are inhospitable to helminth or arthropod invaders [10].
  • IL-10 was not able to compensate for the absence of IL-4/IL-13-activated alternative macrophages [11].
  • Macrophage/neutrophil-specific IL-4 receptor alpha-deficient mice (LysM(Cre)IL-4Ralpha(-/flox)) were generated to understand the role of IL-4/IL-13 responsive myeloid cells during Type 2 immune responses [11].

Chemical compound and disease context of Il13


Biological context of Il13

  • As described in this issue of Immunity, Lee et al. have now used a transgenic mouse assay to identify a locus control region (LCR) that supports integration site-independent, copy number-dependent transcription of Il4 and Il13 [17].
  • Collectively, these findings indicate a novel role of IL-13 in early myelopoiesis, partially overlapping but also different from that of IL-4 [18].
  • To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized [3].
  • However, the mechanisms that induce rapid transactivation of the IL-13 gene in response to various types of stimulation have hitherto remained unknown [19].
  • Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus [20].

Anatomical context of Il13


Associations of Il13 with chemical compounds


Physical interactions of Il13


Regulatory relationships of Il13


Other interactions of Il13


Analytical, diagnostic and therapeutic context of Il13

  • Exogenous administration of interleukin-4 (IL-4) or IL-13 was recently shown to regulate this inflammatory injury in association with activation of signal transducer and activator of transcription-6 (STAT6) [37].
  • In addition, the levels of bioactive and total TGF-beta(1) were decreased in lavage fluids from IL-13 transgenic mice with -/- CCR2 loci [12].
  • To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR [38].
  • Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13 [39].
  • Consistent with these observations, a profound reduction of Th2 cytokine production (IL-5 and IL-13) was detected in the bronchoalveolar lavage fluid (BAL) [40].


  1. Chromatin landscape dynamics of the Il4-Il13 locus during T helper 1 and 2 development. Baguet, A., Bix, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. McKenzie, G.J., Fallon, P.G., Emson, C.L., Grencis, R.K., McKenzie, A.N. J. Exp. Med. (1999) [Pubmed]
  3. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. Zhu, Z., Homer, R.J., Wang, Z., Chen, Q., Geba, G.P., Wang, J., Zhang, Y., Elias, J.A. J. Clin. Invest. (1999) [Pubmed]
  4. Distinct inflammatory mechanisms mediate early versus late colitis in mice. Spencer, D.M., Veldman, G.M., Banerjee, S., Willis, J., Levine, A.D. Gastroenterology (2002) [Pubmed]
  5. Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Chiaramonte, M.G., Cheever, A.W., Malley, J.D., Donaldson, D.D., Wynn, T.A. Hepatology (2001) [Pubmed]
  6. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Fulkerson, P.C., Fischetti, C.A., Rothenberg, M.E. Am. J. Pathol. (2006) [Pubmed]
  7. IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine lung. Zheng, T., Liu, W., Oh, S.Y., Zhu, Z., Hu, B., Homer, R.J., Cohn, L., Grusby, M.J., Elias, J.A. J. Immunol. (2008) [Pubmed]
  8. Intergenic transcription is not required in Th2 cells to maintain histone acetylation and transcriptional permissiveness at the Il4-Il13 locus. Baguet, A., Sun, X., Arroll, T., Krumm, A., Bix, M. J. Immunol. (2005) [Pubmed]
  9. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Akbari, O., Stock, P., Meyer, E., Kronenberg, M., Sidobre, S., Nakayama, T., Taniguchi, M., Grusby, M.J., DeKruyff, R.H., Umetsu, D.T. Nat. Med. (2003) [Pubmed]
  10. Helper T cells regulate type-2 innate immunity in vivo. Shinkai, K., Mohrs, M., Locksley, R.M. Nature (2002) [Pubmed]
  11. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Herbert, D.R., Hölscher, C., Mohrs, M., Arendse, B., Schwegmann, A., Radwanska, M., Leeto, M., Kirsch, R., Hall, P., Mossmann, H., Claussen, B., Förster, I., Brombacher, F. Immunity (2004) [Pubmed]
  12. IL-13-induced chemokine responses in the lung: role of CCR2 in the pathogenesis of IL-13-induced inflammation and remodeling. Zhu, Z., Ma, B., Zheng, T., Homer, R.J., Lee, C.G., Charo, I.F., Noble, P., Elias, J.A. J. Immunol. (2002) [Pubmed]
  13. IL-13 is necessary, not simply sufficient, for epicutaneously induced Th2 responses to soluble protein antigen. Herrick, C.A., Xu, L., McKenzie, A.N., Tigelaar, R.E., Bottomly, K. J. Immunol. (2003) [Pubmed]
  14. Upregulation of interleukin-13 and its receptor in a murine model of bleomycin-induced scleroderma. Matsushita, M., Yamamoto, T., Nishioka, K. Int. Arch. Allergy Immunol. (2004) [Pubmed]
  15. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. Kolodsick, J.E., Toews, G.B., Jakubzick, C., Hogaboam, C., Moore, T.A., McKenzie, A., Wilke, C.A., Chrisman, C.J., Moore, B.B. J. Immunol. (2004) [Pubmed]
  16. Differential regulation by glucocorticoid of interleukin-13-induced eosinophilia, hyperresponsiveness, and goblet cell hyperplasia in mouse airways. Kibe, A., Inoue, H., Fukuyama, S., Machida, K., Matsumoto, K., Koto, H., Ikegami, T., Aizawa, H., Hara, N. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  17. A Th2 cytokine LCR. Adding a new piece to the regulatory puzzle. Smale, S.T. Immunity (2003) [Pubmed]
  18. Interleukin 13: novel role in direct regulation of proliferation and differentiation of primitive hematopoietic progenitor cells. Jacobsen, S.E., Okkenhaug, C., Veiby, O.P., Caput, D., Ferrara, P., Minty, A. J. Exp. Med. (1994) [Pubmed]
  19. The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells. Masuda, A., Yoshikai, Y., Kume, H., Matsuguchi, T. J. Immunol. (2004) [Pubmed]
  20. Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus. Yamashita, M., Ukai-Tadenuma, M., Kimura, M., Omori, M., Inami, M., Taniguchi, M., Nakayama, T. J. Biol. Chem. (2002) [Pubmed]
  21. Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13. Guo, L., Hu-Li, J., Paul, W.E. Immunity (2005) [Pubmed]
  22. Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity. Ansel, K.M., Greenwald, R.J., Agarwal, S., Bassing, C.H., Monticelli, S., Interlandi, J., Djuretic, I.M., Lee, D.U., Sharpe, A.H., Alt, F.W., Rao, A. Nat. Immunol. (2004) [Pubmed]
  23. An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo. Grunewald, S.M., Werthmann, A., Schnarr, B., Klein, C.E., Bröcker, E.B., Mohrs, M., Brombacher, F., Sebald, W., Duschl, A. J. Immunol. (1998) [Pubmed]
  24. Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice. Seto, Y., Nakajima, H., Suto, A., Shimoda, K., Saito, Y., Nakayama, K.I., Iwamoto, I. J. Immunol. (2003) [Pubmed]
  25. Interleukin-4 and -13 inhibit tumor necrosis factor-alpha mRNA translational activation in lipopolysaccharide-induced mouse macrophages. Mijatovic, T., Kruys, V., Caput, D., Defrance, P., Huez, G. J. Biol. Chem. (1997) [Pubmed]
  26. A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages. Coste, A., Linas, M.D., Cassaing, S., Bernad, J., Chalmeton, S., Séguéla, J.P., Pipy, B. J. Antimicrob. Chemother. (2002) [Pubmed]
  27. X-SCID B cell responses to interleukin-4 and interleukin-13 are mediated by a receptor complex that includes the interleukin-4 receptor alpha chain (p140) but not the gamma c chain. Matthews, D.J., Hibbert, L., Friedrich, K., Minty, A., Callard, R.E. Eur. J. Immunol. (1997) [Pubmed]
  28. A 3' enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells. Solymar, D.C., Agarwal, S., Bassing, C.H., Alt, F.W., Rao, A. Immunity (2002) [Pubmed]
  29. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. Kaviratne, M., Hesse, M., Leusink, M., Cheever, A.W., Davies, S.J., McKerrow, J.H., Wakefield, L.M., Letterio, J.J., Wynn, T.A. J. Immunol. (2004) [Pubmed]
  30. Interleukin-13 mediates airways hyperreactivity through the IL-4 receptor-alpha chain and STAT-6 independently of IL-5 and eotaxin. Yang, M., Hogan, S.P., Henry, P.J., Matthaei, K.I., McKenzie, A.N., Young, I.G., Rothenberg, M.E., Foster, P.S. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  31. Interleukin-13 alters the activation state of murine macrophages in vitro: comparison with interleukin-4 and interferon-gamma. Doyle, A.G., Herbein, G., Montaner, L.J., Minty, A.J., Caput, D., Ferrara, P., Gordon, S. Eur. J. Immunol. (1994) [Pubmed]
  32. Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Barner, M., Mohrs, M., Brombacher, F., Kopf, M. Curr. Biol. (1998) [Pubmed]
  33. Interleukin-4-triggered, STAT6-dependent production of a factor that induces mouse mast cell apoptosis. Hu, Z.Q., Zhao, W.H., Shimamura, T., Galli, S.J. Eur. J. Immunol. (2006) [Pubmed]
  34. Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection. Artis, D., Humphreys, N.E., Bancroft, A.J., Rothwell, N.J., Potten, C.S., Grencis, R.K. J. Exp. Med. (1999) [Pubmed]
  35. Fgr deficiency results in defective eosinophil recruitment to the lung during allergic airway inflammation. Vicentini, L., Mazzi, P., Caveggion, E., Continolo, S., Fumagalli, L., Lapinet-Vera, J.A., Lowell, C.A., Berton, G. J. Immunol. (2002) [Pubmed]
  36. Chondroitin sulfate intake inhibits the IgE-mediated allergic response by down-regulating Th2 responses in mice. Sakai, S., Akiyama, H., Sato, Y., Yoshioka, Y., Linhardt, R.J., Goda, Y., Maitani, T., Toida, T. J. Biol. Chem. (2006) [Pubmed]
  37. Regulation of liver inflammatory injury by signal transducer and activator of transcription-6. Kato, A., Yoshidome, H., Edwards, M.J., Lentsch, A.B. Am. J. Pathol. (2000) [Pubmed]
  38. Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. Finkelman, F.D., Yang, M., Perkins, C., Schleifer, K., Sproles, A., Santeliz, J., Bernstein, J.A., Rothenberg, M.E., Morris, S.C., Wills-Karp, M. J. Immunol. (2005) [Pubmed]
  39. Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13. Bessis, N., Boissier, M.C., Ferrara, P., Blankenstein, T., Fradelizi, D., Fournier, C. Eur. J. Immunol. (1996) [Pubmed]
  40. Death receptor-6 regulates the development of pulmonary eosinophilia and airway inflammation in a mouse model of asthma. Venkataraman, C., Justen, K., Zhao, J., Galbreath, E., Na, S. Immunol. Lett. (2006) [Pubmed]
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