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Gene Review

ICOSLG  -  inducible T-cell co-stimulator ligand

Homo sapiens

Synonyms: B7 homolog 2, B7-H2, B7-like protein Gl50, B7-related protein 1, B7H2, ...
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Disease relevance of ICOSLG


High impact information on ICOSLG

  • T-cell co-stimulation through B7RP-1 and ICOS [4].
  • The ligand, which has homology to B7 molecules and is called B7-related protein-1 (B7RP-1), is expressed on B cells and macrophages [4].
  • The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation [5].
  • Although both maturing mDCs and pDCs upregulate the expression of CD80 and CD86, only pDCs upregulate the expression of inducible costimulator ligand (ICOS-L) and maintain high expression levels upon differentiation into mature DCs [6].
  • These IL-10-producing T cells are T regulatory cells, and their generation by ICOS-L is independent of pDC-driven Th1 and Th2 differentiation, although, in the later condition, some contribution from endogenous IL-4 cannot be completely ruled out [6].

Biological context of ICOSLG


Anatomical context of ICOSLG

  • Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha) [11].
  • The human B7RP-1-Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell proliferation in vitro [12].
  • TNF-alpha enhances B7RP-1 expression on B cells and monocytes, while it inhibits it on DC [12].
  • Interestingly, tumor necrosis factor (TNF)-alpha differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC) [12].
  • Taken together, our data suggest an important physiological role of ICOS-L in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue [13].

Associations of ICOSLG with chemical compounds

  • Expression of ICOSL was induced on monocytes after integrin-dependent plastic adhesion [14].
  • Inducible costimulator (ICOS) ligand (ICOSL), a B7-related transmembrane glycoprotein with extracellular IgV and IgC domains, binds to ICOS on activated T cells and delivers a positive costimulatory signal for optimal T cell function [7].
  • The mRNA for perforin was increased in sIBM (28.1 +/- 8.7) compared with controls (4.3 +/- 11.2, P = 0.18), and significantly correlated with mRNA of ICOS, ICOS-L and the degree of endomysial inflammation as assessed in coded haematoxylin/eosin tissue sections [10].

Regulatory relationships of ICOSLG

  • Both ICOSL and CD152L were up-regulated on monocytes by IFN-gamma but by distinct signaling pathways [14].
  • We found that CD34(bright) cells regardless of their myeloid commitment were ICOSL(-), whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared [15].
  • By RT-PCR, RA synovial tissue was shown to express mRNA of B7RP-1 [16].
  • B7-DC and B7-H3 inhibit antigen-stimulated lymphocyte activation while B7-H2 serves in a regulatory capacity, often promoting a Th2 immunophenotype [9].

Other interactions of ICOSLG


Analytical, diagnostic and therapeutic context of ICOSLG


  1. Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo. Schreiner, B., Wischhusen, J., Mitsdoerffer, M., Schneider, D., Bornemann, A., Melms, A., Tolosa, E., Weller, M., Wiendl, H. Glia (2003) [Pubmed]
  2. Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia. Tamura, H., Dan, K., Tamada, K., Nakamura, K., Shioi, Y., Hyodo, H., Wang, S.D., Dong, H., Chen, L., Ogata, K. Clin. Cancer Res. (2005) [Pubmed]
  3. Muscle fibres and cultured muscle cells express the B7.1/2-related inducible co-stimulatory molecule, ICOSL: implications for the pathogenesis of inflammatory myopathies. Wiendl, H., Mitsdoerffer, M., Schneider, D., Melms, A., Lochmuller, H., Hohlfeld, R., Weller, M. Brain (2003) [Pubmed]
  4. T-cell co-stimulation through B7RP-1 and ICOS. Yoshinaga, S.K., Whoriskey, J.S., Khare, S.D., Sarmiento, U., Guo, J., Horan, T., Shih, G., Zhang, M., Coccia, M.A., Kohno, T., Tafuri-Bladt, A., Brankow, D., Campbell, P., Chang, D., Chiu, L., Dai, T., Duncan, G., Elliott, G.S., Hui, A., McCabe, S.M., Scully, S., Shahinian, A., Shaklee, C.L., Van, G., Mak, T.W., Senaldi, G. Nature (1999) [Pubmed]
  5. Treatment of murine lupus with CTLA4Ig. Finck, B.K., Linsley, P.S., Wofsy, D. Science (1994) [Pubmed]
  6. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. Ito, T., Yang, M., Wang, Y.H., Lande, R., Gregorio, J., Perng, O.A., Qin, X.F., Liu, Y.J., Gilliet, M. J. Exp. Med. (2007) [Pubmed]
  7. Structural basis of inducible costimulator ligand costimulatory function: determination of the cell surface oligomeric state and functional mapping of the receptor binding site of the protein. Chattopadhyay, K., Bhatia, S., Fiser, A., Almo, S.C., Nathenson, S.G. J. Immunol. (2006) [Pubmed]
  8. Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus. Hutloff, A., Büchner, K., Reiter, K., Baelde, H.J., Odendahl, M., Jacobi, A., Dörner, T., Kroczek, R.A. Arthritis Rheum. (2004) [Pubmed]
  9. The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta. Petroff, M.G., Kharatyan, E., Torry, D.S., Holets, L. Am. J. Pathol. (2005) [Pubmed]
  10. Upregulated inducible co-stimulator (ICOS) and ICOS-ligand in inclusion body myositis muscle: significance for CD8+ T cell cytotoxicity. Schmidt, J., Rakocevic, G., Raju, R., Dalakas, M.C. Brain (2004) [Pubmed]
  11. LICOS, a primordial costimulatory ligand? Brodie, D., Collins, A.V., Iaboni, A., Fennelly, J.A., Sparks, L.M., Xu, X.N., van der Merwe, P.A., Davis, S.J. Curr. Biol. (2000) [Pubmed]
  12. Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS. Yoshinaga, S.K., Zhang, M., Pistillo, J., Horan, T., Khare, S.D., Miner, K., Sonnenberg, M., Boone, T., Brankow, D., Dai, T., Delaney, J., Han, H., Hui, A., Kohno, T., Manoukian, R., Whoriskey, J.S., Coccia, M.A. Int. Immunol. (2000) [Pubmed]
  13. ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells. Khayyamian, S., Hutloff, A., Büchner, K., Gräfe, M., Henn, V., Kroczek, R.A., Mages, H.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. Characterization of human inducible costimulator ligand expression and function. Aicher, A., Hayden-Ledbetter, M., Brady, W.A., Pezzutto, A., Richter, G., Magaletti, D., Buckwalter, S., Ledbetter, J.A., Clark, E.A. J. Immunol. (2000) [Pubmed]
  15. Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34(+) progenitor cells during differentiation into antigen presenting cells. Richter, G., Hayden-Ledbetter, M., Irgang, M., Ledbetter, J.A., Westermann, J., Körner, I., Daemen, K., Clark, E.A., Aicher, A., Pezzutto, A. J. Biol. Chem. (2001) [Pubmed]
  16. Expression and function of the co-stimulator H4/ICOS on activated T cells of patients with rheumatoid arthritis. Okamoto, T., Saito, S., Yamanaka, H., Tomatsu, T., Kamatani, N., Ogiuchi, H., Uchiyama, T., Yagi, J. J. Rheumatol. (2003) [Pubmed]
  17. Expression of Costimulatory Molecules on Human Retinoblastoma Cells Y-79: Functional Expression of CD40 and B7H1. Usui, Y., Okunuki, Y., Hattori, T., Takeuchi, M., Kezuka, T., Goto, H., Usui, M. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  18. Expression of the costimulatory molecule B7-H2 (inducible costimulator ligand) by human airway epithelial cells. Kurosawa, S., Myers, A.C., Chen, L., Wang, S., Ni, J., Plitt, J.R., Heller, N.M., Bochner, B.S., Schleimer, R.P. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
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