Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity
10.1126/science.287.5454.860
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus–type 1 (KOS strain)] and bacterial infection ( Listeria monocytogenes ) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-γ production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.

Bibliography

Ashkar, S., Weber, G. F., Panoutsakopoulou, V., Sanchirico, M. E., Jansson, M., Zawaideh, S., Rittling, S. R., Denhardt, D. T., Glimcher, M. J., & Cantor, H. (2000). Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity. Science, 287(5454), 860–864.

Authors 10
  1. Samy Ashkar (first)
  2. Georg F. Weber (additional)
  3. Vassiliki Panoutsakopoulou (additional)
  4. Marie E. Sanchirico (additional)
  5. Marianne Jansson (additional)
  6. Samer Zawaideh (additional)
  7. Susan R. Rittling (additional)
  8. David T. Denhardt (additional)
  9. Melvin J. Glimcher (additional)
  10. Harvey Cantor (additional)
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  69. Supported in part by NIH research grants AI12184 AI37833 (to H.C.) CA76176 (to G.F.W.) and AR34078 (to M.J.G.); grants AR44434 DC01295 ES06897 (to D.T.D.) and CA72740 (to S.R.R.) for development of Opn-null mice at Rutgers University; U.S. Department of Defense breast cancer grants DAMD17-98-1-8060 (to G.F.W.) and DAMD 17-99-1-9124 (to S.A.); U.S. Department of Public Health grant 340B9930002 and Biomorphics (to S.A.); the Fulbright Foundation (to S.Z.); and the Swedish Foundation for International Cooperation in Research and Higher Education (to M.J.). All experimentation involving animals was in accordance with Dana-Farber institutional guidelines. We thank T. W. Mak for CD44 −/− mice; B. J. Rollins for L. monocytogenes strain 1778; S. Hikita and D. Block for technical assistance; and A. Angel K. MacKay and L. Lagasse for assistance in the preparation of the manuscript.
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:48 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 4:58 a.m.)
Indexed 3 weeks, 5 days ago (Aug. 2, 2025, 12:07 a.m.)
Issued 25 years, 6 months ago (Feb. 4, 2000)
Published 25 years, 6 months ago (Feb. 4, 2000)
Published Print 25 years, 6 months ago (Feb. 4, 2000)
Funders 0

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@article{Ashkar_2000, title={Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity}, volume={287}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.287.5454.860}, DOI={10.1126/science.287.5454.860}, number={5454}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Ashkar, Samy and Weber, Georg F. and Panoutsakopoulou, Vassiliki and Sanchirico, Marie E. and Jansson, Marianne and Zawaideh, Samer and Rittling, Susan R. and Denhardt, David T. and Glimcher, Melvin J. and Cantor, Harvey}, year={2000}, month=feb, pages={860–864} }