The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Icosl  -  icos ligand

Mus musculus

Synonyms: AU044799, B7 homolog 2, B7-H2, B7-like protein Gl50, B7-related protein 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Icosl


High impact information on Icosl


Chemical compound and disease context of Icosl

  • All three diethyl esters inhibit the growth of L1210 murine leukemia and B16 melanotic melanoma in culture, with GI50 values in the micromolar concentration range [8].
  • When the aromatic portion of the molecule is a fused heterobicyclic structure (e.g., benzothiazole derivative 7a), potent in vitro antitumor activity was observed in HCT 116 (GI50 = 40 nM) and HT 29 (GI50 = 380 nM) human colon as well in as MCF-7 and MDA 468 human breast cancer cell lines [9].
  • Pomolic acid was the most cytotoxic component, and was specific for M-14 melanoma and ME180 cervical carcinoma, with GI50 values of 6.9 and 8.3 micrograms/mL respectively [10].
  • Very strong growth inhibition of 1,6-DPD/OH/NH2 was observed against one leukemia line (HL-60(TB)), one NSCLC line (HOP-92), one ovarian cancer line (OVCAR-8) and one breast cancer line (T-47D) with GI50 <1.0 microM, i.e. 0.50, 0.85, 0.62 and 0.75 microM, respectively [11].

Biological context of Icosl

  • Further studies reveal that Type I IFN are general suppressors of TLR-mediated up-regulation of B7RP-1 [12].
  • Administration of anti-B7h mAb significantly ameliorated the disease as assessed by clinical arthritis score and histology in the joints, and a beneficial effect was also obtained by a delayed treatment after the onset of disease [1].
  • Interaction of B7RP-1 with ICOS negatively regulates antigen presentation by B cells [13].
  • During antigen-specific B cell activation, costimulation through CD40 signaling can reverse both BCR- and IL-4R-mediated B7h down-regulation [14].
  • These data suggest that ICOS/B7RP-1 interactions may not affect the organogenesis, but involve in the functional development of PPs [15].

Anatomical context of Icosl

  • These data define a novel costimulatory ligand for T cells and suggest that induction of B7h by TNFalpha may function as a mechanism to directly augment recognition of self during inflammation [16].
  • Surprisingly, although B7h is expressed in unstimulated B cells, its expression is induced in both 3T3 cells and embryonic fibroblasts treated with TNFalpha, and it is upregulated in nonlymphoid tissues of mice treated with LPS, a potent activator of TNFalpha [16].
  • Costimulation through the inducible costimulator (ICOS) and its ligand (ICOSL) is essential for T cell-dependent B cell responses, but the cellular and temporal dynamics underlying its in vivo effects are poorly defined [17].
  • The ICOS-ligand B7-H2, expressed on human type II alveolar epithelial cells, plays a role in the pulmonary host defense system [18].
  • Although it is known that blockade of ICOS-B7-related protein 1 (B7RP-1) in vivo dramatically reduces germinal center formation and Ab production, the mechanism(s) remains unclear [19].

Associations of Icosl with chemical compounds

  • Evodiamine inhibited the proliferation of NCI/ADR-RES cells in a concentration-dependent manner with a GI50 of 0.59 +/- 0.11 microM [20].
  • The 2-phenyl-1,8-naphthyridin-4-ones (44-49) with a methoxy group at the 3'-position showed potent cytotoxicity against most tumor cell lines with GI50 values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen [21].
  • Incubation of L1210 cells with the sulfoxide in vitro results in a rapid increase in the intracellular concentration of the glyoxalase I inhibitor (kapp = 1. 41 +/- 0.03 min-1 (37 degrees C)) and inhibition of cell growth (GI50 = 0.5 +/- 0.1 microM) [22].
  • In comparison to a standard cytotoxic agent such as doxorubicin (GI50 = 45.3 nM), 3 (GI50 = 17.9 nM) inhibited LNCaP cell growth more potently [23].
  • 1 (AJM3/23), 2 (GHP-TM-III-07w), and 3 (GHP-KB-06) inhibited cell growth with 3 being the most potent in C1A (GI50 = 18.0 nM), C2H (GI50 = 17.0 nM), and LNCaP (GI50 = 17.9 nM) cells [23].

Regulatory relationships of Icosl

  • In conclusion, the B7RP-1/ICOS pathway is negatively regulating T cell activation by B cells and may play a role similar to that of the PD-L1/PD-1 pathway [13].
  • Unexpectedly, blocking antibodies for B7RP-1 and ICOS enhanced the IL-2 response in both T cells [13].
  • CONCLUSIONS: These data show that the B7RP-1/ICOS interaction inhibits Th1 and Th2 T-cell responses in the setting of foreign antigen presentation by renal TECs [24].
  • These findings suggest that the ICOS-B7RP-1 costimulatory pathway serves primarily to control IFN-gamma production, thereby promoting a cytokine environment conducive to limited hepatic damage [25].
  • Overall, the data demonstrate a critical role played by ICOS-L-expressing and IL-10-producing DCs from Chlamydia-infected mice in the infection-mediated inhibition of allergic responses [26].

Other interactions of Icosl

  • We studied the efficacy of systemic treatment of tumors with murine B7.2-IgG or GL50-IgG fusion proteins, and the therapeutic potential of B7.1 or GL50 vaccines given during various phases of the antitumor responses [27].
  • B7h can costimulate proliferation of purified T cells through a receptor on T cells distinct from CD28 or CTLA-4 [16].
  • Exploiting the adoptive transfer of T or B cells from primed Icosl(-/-) mice, we provided genetic evidence that costimulation through ICOSL was essential for primary but not secondary helper T cell responses and for the control of both T and B cell activities, resulting in T cell-dependent IgG1 production [17].
  • Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation [12].
  • Blockade of B7RP-1/ICOS lead to an increased IFN-gamma response in Th1 cells (A.E7) and an increased IL-4 response in Th2 cells (D10.G4.1) [13].

Analytical, diagnostic and therapeutic context of Icosl


  1. Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homologous protein costimulation. Iwai, H., Kozono, Y., Hirose, S., Akiba, H., Yagita, H., Okumura, K., Kohsaka, H., Miyasaka, N., Azuma, M. J. Immunol. (2002) [Pubmed]
  2. Renal tubular epithelial expression of the costimulatory molecule B7RP-1 (inducible costimulator ligand). Wahl, P., Schoop, R., Bilic, G., Neuweiler, J., Le Hir, M., Yoshinaga, S.K., Wüthrich, R.P. J. Am. Soc. Nephrol. (2002) [Pubmed]
  3. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Akbari, O., Freeman, G.J., Meyer, E.H., Greenfield, E.A., Chang, T.T., Sharpe, A.H., Berry, G., DeKruyff, R.H., Umetsu, D.T. Nat. Med. (2002) [Pubmed]
  4. ICOS-B7 homologous protein interactions are necessary for mercury-induced autoimmunity. Zheng, Y., Jost, M., Gaughan, J.P., Class, R., Coyle, A.J., Monestier, M. J. Immunol. (2005) [Pubmed]
  5. Bacterial probiotic modulation of dendritic cells. Drakes, M., Blanchard, T., Czinn, S. Infect. Immun. (2004) [Pubmed]
  6. ICOS is essential for effective T-helper-cell responses. Tafuri, A., Shahinian, A., Bladt, F., Yoshinaga, S.K., Jordana, M., Wakeham, A., Boucher, L.M., Bouchard, D., Chan, V.S., Duncan, G., Odermatt, B., Ho, A., Itie, A., Horan, T., Whoriskey, J.S., Pawson, T., Penninger, J.M., Ohashi, P.S., Mak, T.W. Nature (2001) [Pubmed]
  7. ICOS co-stimulatory receptor is essential for T-cell activation and function. Dong, C., Juedes, A.E., Temann, U.A., Shresta, S., Allison, J.P., Ruddle, N.H., Flavell, R.A. Nature (2001) [Pubmed]
  8. Mechanism-based competitive inhibitors of glyoxalase I: intracellular delivery, in vitro antitumor activities, and stabilities in human serum and mouse serum. Kavarana, M.J., Kovaleva, E.G., Creighton, D.J., Wollman, M.B., Eiseman, J.L. J. Med. Chem. (1999) [Pubmed]
  9. 4-Substituted 4-hydroxycyclohexa-2,5-dien-1-ones with selective activities against colon and renal cancer cell lines. Wells, G., Berry, J.M., Bradshaw, T.D., Burger, A.M., Seaton, A., Wang, B., Westwell, A.D., Stevens, M.F. J. Med. Chem. (2003) [Pubmed]
  10. Cytotoxic triterpene acids from the Peruvian medicinal plant Polylepis racemosa. Neto, C.C., Vaisberg, A.J., Zhou, B.N., Kingston, D.G., Hammond, G.B. Planta Med. (2000) [Pubmed]
  11. Induction of growth inhibition and G1 arrest in human cancer cell lines by relatively low-toxic diamantane derivatives. Wang, J.J., Huang, K.T., Chern, Y.T. Anticancer Drugs (2004) [Pubmed]
  12. Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation. Zhou, Z., Hoebe, K., Du, X., Jiang, Z., Shamel, L., Beutler, B. Eur. J. Immunol. (2005) [Pubmed]
  13. Interaction of B7RP-1 with ICOS negatively regulates antigen presentation by B cells. Wahl, P., Schoop, R., Horan, T.P., Yoshinaga, S.K., Wüthrich, R.P. Inflammation (2003) [Pubmed]
  14. Constitutive expression of the B7h ligand for inducible costimulator on naive B cells is extinguished after activation by distinct B cell receptor and interleukin 4 receptor-mediated pathways and can be rescued by CD40 signaling. Liang, L., Porter, E.M., Sha, W.C. J. Exp. Med. (2002) [Pubmed]
  15. The role of inducible co-stimulator (ICOS)/B7-related protein-1 (B7RP-1) interaction in the functional development of Peyer's patches. Iiyama, R., Kanai, T., Uraushihara, K., Totsuka, T., Nakamura, T., Miyata, T., Yagita, H., Kushi, A., Suzuki, K., Tezuka, K., Watanabe, M. Immunol. Lett. (2003) [Pubmed]
  16. B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha. Swallow, M.M., Wallin, J.J., Sha, W.C. Immunity (1999) [Pubmed]
  17. Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses. Mak, T.W., Shahinian, A., Yoshinaga, S.K., Wakeham, A., Boucher, L.M., Pintilie, M., Duncan, G., Gajewska, B.U., Gronski, M., Eriksson, U., Odermatt, B., Ho, A., Bouchard, D., Whorisky, J.S., Jordana, M., Ohashi, P.S., Pawson, T., Bladt, F., Tafuri, A. Nat. Immunol. (2003) [Pubmed]
  18. The ICOS-ligand B7-H2, expressed on human type II alveolar epithelial cells, plays a role in the pulmonary host defense system. Qian, X., Agematsu, K., Freeman, G.J., Tagawa, Y., Sugane, K., Hayashi, T. Eur. J. Immunol. (2006) [Pubmed]
  19. Inducible costimulatory molecule-B7-related protein 1 interactions are important for the clonal expansion and B cell helper functions of naive, Th1, and Th2 T cells. Smith, K.M., Brewer, J.M., Webb, P., Coyle, A.J., Gutierrez-Ramos, C., Garside, P. J. Immunol. (2003) [Pubmed]
  20. Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo. Liao, C.H., Pan, S.L., Guh, J.H., Chang, Y.L., Pai, H.C., Lin, C.H., Teng, C.M. Carcinogenesis (2005) [Pubmed]
  21. Antitumor agents. 174. 2',3',4',5,6,7-Substituted 2-phenyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. Chen, K., Kuo, S.C., Hsieh, M.C., Mauger, A., Lin, C.M., Hamel, E., Lee, K.H. J. Med. Chem. (1997) [Pubmed]
  22. A new method for rapidly generating inhibitors of glyoxalase I inside tumor cells using S-(N-aryl-N-hydroxycarbamoyl)ethylsulfoxides. Hamilton, D.S., Kavarana, M.J., Sharkey, E.M., Eiseman, J.L., Creighton, D.J. J. Med. Chem. (1999) [Pubmed]
  23. Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in prostate cancer cell lines. Alagbala, A.A., McRiner, A.J., Borstnik, K., Labonte, T., Chang, W., D'Angelo, J.G., Posner, G.H., Foster, B.A. J. Med. Chem. (2006) [Pubmed]
  24. Role of the B7RP-1/ICOS pathway in renal tubular epithelial antigen presentation to CD4+ Th1 and Th2 cells. Wahl, P., Wüthrich, R.P. Nephron Exp. Nephrol. (2004) [Pubmed]
  25. Disruption of the ICOS-B7RP-1 costimulatory pathway leads to enhanced hepatic immunopathology and increased gamma interferon production by CD4 T cells in murine schistosomiasis. Rutitzky, L.I., Ozkaynak, E., Rottman, J.B., Stadecker, M.J. Infect. Immun. (2003) [Pubmed]
  26. Chlamydia Infection Induces ICOS Ligand-Expressing and IL-10-Producing Dendritic Cells That Can Inhibit Airway Inflammation and Mucus Overproduction Elicited by Allergen Challenge in BALB/c Mice. Han, X., Wang, S., Fan, Y., Yang, J., Jiao, L., Qiu, H., Yang, X. J. Immunol. (2006) [Pubmed]
  27. Comparable in vivo efficacy of CD28/B7, ICOS/GL50, and ICOS/GL50B costimulatory pathways in murine tumor models: IFNgamma-dependent enhancement of CTL priming, effector functions, and tumor specific memory CTL. Zuberek, K., Ling, V., Wu, P., Ma, H.L., Leonard, J.P., Collins, M., Dunussi-Joannopoulos, K. Cell. Immunol. (2003) [Pubmed]
  28. The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity. Harada, H., Salama, A.D., Sho, M., Izawa, A., Sandner, S.E., Ito, T., Akiba, H., Yagita, H., Sharpe, A.H., Freeman, G.J., Sayegh, M.H. J. Clin. Invest. (2003) [Pubmed]
  29. The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. Akiba, H., Takeda, K., Kojima, Y., Usui, Y., Harada, N., Yamazaki, T., Ma, J., Tezuka, K., Yagita, H., Okumura, K. J. Immunol. (2005) [Pubmed]
  30. Molecular cloning and characterization of murine ICOS and identification of B7h as ICOS ligand. Mages, H.W., Hutloff, A., Heuck, C., Büchner, K., Himmelbauer, H., Oliveri, F., Kroczek, R.A. Eur. J. Immunol. (2000) [Pubmed]
WikiGenes - Universities