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Il27  -  interleukin 27

Mus musculus

Synonyms: IL-27, IL-27 subunit alpha, IL-27-A, IL-27p28, IL27-A, ...
 
 
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Disease relevance of Il27

 

High impact information on Il27

  • We show here that the complement-derived C5a anaphylatoxin negatively regulates TLR4- and CD40-induced synthesis of IL-12 family cytokines (IL-12, IL-23, and IL-27) from inflammatory macrophages (M phi s) by extracellular signal-regulated kinase- and phosphoinositide 3 kinase-dependent pathways [5].
  • Although recent studies have described IL-27 and its receptor, WSX-1, as promoters of Th1 differentiation in naive CD4+ T cells, the data presented here indicate that signaling through this receptor is involved in limiting the intensity and duration of T cell activity [6].
  • Finally, IL-27 suppressed IL-6-mediated T cell proliferation [3].
  • Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system [7].
  • In this study, we investigated the transcriptional regulation of the mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and interferon (IFN)-gamma [8].
 

Biological context of Il27

 

Anatomical context of Il27

 

Associations of Il27 with chemical compounds

 

Physical interactions of Il27

 

Regulatory relationships of Il27

  • The IL-27-induced IgG2a class switching is highly dependent on T-bet in response to T-independent stimuli such as LPS [9].
  • Previous reports have focused on the ability of IL-27 to promote naive T cell responses but the present study reveals that surface expression of WSX-1, the ligand-specific component of the IL-27R, is low on these cells and that highest levels are found on effector and memory CD4(+) and CD8(+) T cells [13].
  • We also found that antitumor effects of B16/IL-23 and B16/IL-27 were synergistically enhanced by treatment with IL-18 and IL-12, respectively [16].
  • In addition, IL-27 directly suppressed CD4+ T cell proliferation and Th2 cytokine production [17].
 

Other interactions of Il27

  • Expression of WSX-1, one subunit of IL-27R, was detected at the mRNA level in primary mouse spleen B cells, and stimulation of these B cells by IL-27 rapidly activated STAT1 [9].
  • We here show a role for IL-27 in the induction of T-bet expression and regulation of Ig class switching in B cells [9].
  • Correlated with the inhibition, IL-27 was shown to augment SOCS3 expression [18].
  • IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signaling 3 [18].
  • IL-27 is a recently defined family member of the long-chain, four-helix bundle cytokines, which consist of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide [19].
 

Analytical, diagnostic and therapeutic context of Il27

References

  1. IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis. Li, J., Gran, B., Zhang, G.X., Rostami, A., Kamoun, M. J. Neurol. Sci. (2005) [Pubmed]
  2. Plasmid interleukin-23 (IL-23), but not plasmid IL-27, enhances the protective efficacy of a DNA vaccine against Mycobacterium tuberculosis infection. Wozniak, T.M., Ryan, A.A., Triccas, J.A., Britton, W.J. Infect. Immun. (2006) [Pubmed]
  3. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Batten, M., Li, J., Yi, S., Kljavin, N.M., Danilenko, D.M., Lucas, S., Lee, J., de Sauvage, F.J., Ghilardi, N. Nat. Immunol. (2006) [Pubmed]
  4. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. Wirtz, S., Tubbe, I., Galle, P.R., Schild, H.J., Birkenbach, M., Blumberg, R.S., Neurath, M.F. J. Exp. Med. (2006) [Pubmed]
  5. C5a negatively regulates toll-like receptor 4-induced immune responses. Hawlisch, H., Belkaid, Y., Baelder, R., Hildeman, D., Gerard, C., Köhl, J. Immunity (2005) [Pubmed]
  6. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Villarino, A., Hibbert, L., Lieberman, L., Wilson, E., Mak, T., Yoshida, H., Kastelein, R.A., Saris, C., Hunter, C.A. Immunity (2003) [Pubmed]
  7. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Stumhofer, J.S., Laurence, A., Wilson, E.H., Huang, E., Tato, C.M., Johnson, L.M., Villarino, A.V., Huang, Q., Yoshimura, A., Sehy, D., Saris, C.J., O'shea, J.J., Hennighausen, L., Ernst, M., Hunter, C.A. Nat. Immunol. (2006) [Pubmed]
  8. Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-{gamma}-mediated pathways. Liu, J., Guan, X., Ma, X. J. Exp. Med. (2007) [Pubmed]
  9. Induction of IgG2a class switching in B cells by IL-27. Yoshimoto, T., Okada, K., Morishima, N., Kamiya, S., Owaki, T., Asakawa, M., Iwakura, Y., Fukai, F., Mizuguchi, J. J. Immunol. (2004) [Pubmed]
  10. IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., Khader, S.A., Solache, A., Gilmartin, L., Ghilardi, N., deSauvage, F., Cooper, A.M. J. Immunol. (2004) [Pubmed]
  11. Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells. Zhang, J.H., He, H., Borzychowski, A.M., Takeda, K., Akira, S., Croy, B.A. Biol. Reprod. (2003) [Pubmed]
  12. Expression of IL-27 in human Th1-associated granulomatous diseases. Larousserie, F., Pflanz, S., Coulomb-L'Herminé, A., Brousse, N., Kastelein, R., Devergne, O. J. Pathol. (2004) [Pubmed]
  13. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. Villarino, A.V., Larkin, J., Saris, C.J., Caton, A.J., Lucas, S., Wong, T., de Sauvage, F.J., Hunter, C.A. J. Immunol. (2005) [Pubmed]
  14. WSX-1 over-expression in CD4(+) T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation. Takeda, A., Hamano, S., Shiraishi, H., Yoshimura, T., Ogata, H., Ishii, K., Ishibashi, T., Yoshimura, A., Yoshida, H. Int. Immunol. (2005) [Pubmed]
  15. IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. Molle, C., Nguyen, M., Flamand, V., Renneson, J., Trottein, F., De Wit, D., Willems, F., Goldman, M., Goriely, S. J. Immunol. (2007) [Pubmed]
  16. Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Oniki, S., Nagai, H., Horikawa, T., Furukawa, J., Belladonna, M.L., Yoshimoto, T., Hara, I., Nishigori, C. Cancer Res. (2006) [Pubmed]
  17. The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. Artis, D., Villarino, A., Silverman, M., He, W., Thornton, E.M., Mu, S., Summer, S., Covey, T.M., Huang, E., Yoshida, H., Koretzky, G., Goldschmidt, M., Wu, G.D., de Sauvage, F., Miller, H.R., Saris, C.J., Scott, P., Hunter, C.A. J. Immunol. (2004) [Pubmed]
  18. IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signaling 3. Owaki, T., Asakawa, M., Kamiya, S., Takeda, K., Fukai, F., Mizuguchi, J., Yoshimoto, T. J. Immunol. (2006) [Pubmed]
  19. Suppression of ongoing experimental autoimmune encephalomyelitis by neutralizing the function of the p28 subunit of IL-27. Goldberg, R., Zohar, Y., Wildbaum, G., Geron, Y., Maor, G., Karin, N. J. Immunol. (2004) [Pubmed]
  20. Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations. Sonobe, Y., Yawata, I., Kawanokuchi, J., Takeuchi, H., Mizuno, T., Suzumura, A. Brain Res. (2005) [Pubmed]
  21. Rapid phosphorylation of 28-kDa heat-shock protein by treatment with okadaic acid and phorbol ester of BALB/MK-2 mouse keratinocytes. Kasahara, K., Ikuta, T., Chida, K., Asakura, R., Kuroki, T. Eur. J. Biochem. (1993) [Pubmed]
  22. Intracellular localization and protein interactions of the gene 1 protein p28 during mouse hepatitis virus replication. Brockway, S.M., Lu, X.T., Peters, T.R., Dermody, T.S., Denison, M.R. J. Virol. (2004) [Pubmed]
 
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