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Science 4 February 2000:
Vol. 287. no. 5454, pp. 860 - 864
DOI: 10.1126/science.287.5454.860
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Reports

Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity

Samy Ashkar, 1* Georg F. Weber, 23*dagger Vassiliki Panoutsakopoulou, 24 Marie E. Sanchirico, 24 Marianne Jansson, 24 Samer Zawaideh, 1 Susan R. Rittling, 5 David T. Denhardt, 5 Melvin J. Glimcher, 1 Harvey Cantor 24ddagger

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-gamma 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.

1 Laboratory for Skeletal Disorders and Rehabilitation, Department of Orthopedic Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute;
3 Department of Medicine;
4 Department of Pathology; Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
5 Faculty of Arts and Sciences, Division of Life Sciences, Rutgers University, 604 Allison Road, NJ 08854, USA.
*   These authors contributed equally to this work.

dagger    Present address: Division of Radiation and Cancer Biology, New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.

ddagger    To whom correspondence should be addressed. E-mail: Harvey_Cantor{at}DFCI.harvard.edu

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PNAS 101, 12969-12973
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Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model.
A. Sahai, P. Malladi, H. Melin-Aldana, R. M. Green, and P. F. Whitington (2004)
Am J Physiol Gastrointest Liver Physiol 287, G264-G273
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Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells.
M. Iwata, N. Awaya, L. Graf, C. Kahl, and B. Torok-Storb (2004)
Blood 103, 4496-4502
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Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice.
J. S. Berman, D. Serlin, X. Li, G. Whitley, J. Hayes, D. C. Rishikof, D. A. Ricupero, L. Liaw, M. Goetschkes, and A. W. O'Regan (2004)
Am J Physiol Lung Cell Mol Physiol 286, L1311-L1318
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Osteopontin affects the persistence of {beta}-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms.
J. Morimoto, M. Inobe, C. Kimura, S. Kon, H. Diao, M. Aoki, T. Miyazaki, D. T. Denhardt, S. Rittling, and T. Uede (2004)
Int. Immunol. 16, 477-488
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Osteopontin But Not Osteonectin Messenger RNA Expression Is a Prognostic Marker in Curatively Resected Non-Small Cell Lung Cancer.
S. Schneider, J. Yochim, J. Brabender, K. Uchida, K. D. Danenberg, R. Metzger, P. M. Schneider, D. Salonga, A. H. Holscher, and P. V. Danenberg (2004)
Clin. Cancer Res. 10, 1588-1596
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High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation.
A. Chiocchetti, M. Indelicato, T. Bensi, R. Mesturini, M. Giordano, S. Sametti, L. Castelli, F. Bottarel, M. C. Mazzarino, L. Garbarini, et al. (2004)
Blood 103, 1376-1382
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Effect of Osteopontin Alleles on {beta}-Glucan-Induced Granuloma Formation in the Mouse Liver.
K. Tanaka, J. Morimoto, S. Kon, C. Kimura, M. Inobe, H. Diao, G. Hirschfeld, J. M. Weiss, and T. Uede (2004)
Am. J. Pathol. 164, 567-575
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Toxicogenomic Approach to Endocrine Disrupters: Identification of a Transcript Profile Characteristic of Chemicals with Estrogenic Activity.
J. M. Naciff and G. P. Daston (2004)
Toxicol Pathol 32, 59-70
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Osteopontin: Roles in Implantation and Placentation.
G. A. Johnson, R. C. Burghardt, F. W. Bazer, and T. E. Spencer (2003)
Biol Reprod 69, 1458-1471
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The graft response to transplantation: a gene expression profile analysis.
K. Christopher, T. F. Mueller, R. DeFina, Y. Liang, J. Zhang, R. Gentleman, and D. L. Perkins (2003)
Physiol Genomics 15, 52-64
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Osteopontin (Eta-1) and Fibroblast Growth Factor-2 Cross-Talk in Angiogenesis.
D. Leali, P. Dell'Era, H. Stabile, B. Sennino, A. F. Chambers, A. Naldini, S. Sozzani, B. Nico, D. Ribatti, and M. Presta (2003)
J. Immunol. 171, 1085-1093
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Expression Profiling of Cytokines and Related Genes in Regenerating Skeletal Muscle after Cardiotoxin Injection: A Role for Osteopontin.
A. Hirata, S. Masuda, T. Tamura, K. Kai, K. Ojima, A. Fukase, K. Motoyoshi, K. Kamakura, Y. Miyagoe-Suzuki, and S.'i. Takeda (2003)
Am. J. Pathol. 163, 203-215
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Alterations of Arterial Physiology in Osteopontin-Null Mice.
D. L. Myers, K. J. Harmon, V. Lindner, and L. Liaw (2003)
Arterioscler. Thromb. Vasc. Biol. 23, 1021-1028
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Osteopontin Deficiency Attenuates Atherosclerosis in Female Apolipoprotein E-Deficient Mice.
Y. Matsui, S. R. Rittling, H. Okamoto, M. Inobe, N. Jia, T. Shimizu, M. Akino, T. Sugawara, J. Morimoto, C. Kimura, et al. (2003)
Arterioscler. Thromb. Vasc. Biol. 23, 1029-1034
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Osteopontin Expression in Uterine Stroma Indicates a Decidualization-Like Differentiation During Ovine Pregnancy.
G. A. Johnson, R. C. Burghardt, M. M. Joyce, T. E. Spencer, F. W. Bazer, C. Pfarrer, and C. A. Gray (2003)
Biol Reprod 68, 1951-1958
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High Plasma Osteopontin Level and Its Relationship with Interleukin-12-mediated Type 1 T Helper Cell Response in Tuberculosis.
Y. Koguchi, K. Kawakami, K. Uezu, K. Fukushima, S. Kon, M. Maeda, A. Nakamoto, I. Owan, M. Kuba, N. Kudeken, et al. (2003)
Am. J. Respir. Crit. Care Med. 167, 1355-1359
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Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment.
E. J. Wherry, J. N. Blattman, K. Murali-Krishna, R. van der Most, and R. Ahmed (2003)
J. Virol. 77, 4911-4927
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Gene Expression Profile Induced by 17{alpha}-Ethynyl Estradiol in the Prepubertal Female Reproductive System of the Rat.
J. M. Naciff, G. J. Overmann, S. M. Torontali, G. J. Carr, J. P. Tiesman, B. D. Richardson, and G. P. Daston (2003)
Toxicol. Sci. 72, 314-330
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