DOI: 10.1073/pnas.0508666102. T-bet-dependent expression of osteopontin contributes to T cell polarization

T-bet-dependent expression of osteopontin contributes to T cell polarization

10.1073/pnas.0508666102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The osteopontin (Opn) glycoprotein has been implicated in diverse physiological processes, including vascularization, bone formation, and inflammatory responses. Studies of its role in immune responses has suggested that Opn can set the early stage of type-1 immune (cell-mediated) responses through differential regulation of IL-12 and IL-10 cytokine gene expression in macrophages. Although Opn has been suggested to play a role in the development of type-1 immunity, little is known about control of Opn gene expression. Here, we report that Opn gene expression in activated T cells, but not macrophages, is regulated by T-bet, a transcription factor that controls CD4 + T helper (Th1) cell lineage commitment. We also find that T-bet-dependent expression of Opn in T cells is essential for efficient skewing of CD4 + T and CD8 + T cells toward the Th1 and type 1 CD8 + T cells (Tc1) pathway, respectively. Taken together, these findings begin to delineate the genetic basis of Opn expression in T cells and further clarify the role of Opn in Th and Tc1 development.

Bibliography

Shinohara, M. L., Jansson, M., Hwang, E. S., Werneck, M. B. F., Glimcher, L. H., & Cantor, H. (2005). T-bet-dependent expression of osteopontin contributes to T cell polarization. Proceedings of the National Academy of Sciences, 102(47), 17101â17106.

Authors 6

Mari L. Shinohara (first)
Marianne Jansson (additional)
Eun Sook Hwang (additional)
Miriam B. F. Werneck (additional)
Laurie H. Glimcher (additional)
Harvey Cantor (additional)

References 29 Referenced 123

10.1016/S0167-5699(00)01715-1
10.1172/JCI12980
Weber, G. F. & Cantor, H. (2001) Clin. Exp. Immunol. 126, 578-583.11737079 / Clin. Exp. Immunol. (2001)
10.1126/science.287.5454.860
10.1128/JVI.79.6.3509-3516.2005
10.1016/S0002-9440(10)64514-2
10.1136/gut.2004.048298
10.1126/science.1062960
10.4049/jimmunol.168.5.2096
10.1146/annurev.neuro.25.112701.142913
10.1172/JCI200523273
10.1161/01.ATV.0000074878.29805.D0
10.1172/JCI18141
10.1182/blood-2004-08-3228
10.1016/S0092-8674(00)80702-3
10.1073/pnas.2636938100
10.1073/pnas.1332767100
10.1073/pnas.261570598
10.1038/ni794
10.1016/S0022-1759(02)00424-6
10.1016/S1074-7613(00)80671-8
10.1126/science.1103336
Blom, T., Franzen, A., Heinegard, D. & Holmdahl, R. (2003) Science 299, 1845.12649465 / Science (2003)
Scott, J. A., Weir, M. L., Wilson, S. M., Xuan, J. W., Chambers, A. F. & McCormack, D. G. (1998) Am. J. Physiol. 275, H2258-H2265.9843827 / Am. J. Physiol. (1998)
10.1128/IAI.70.3.1042-1048.2002
10.1016/j.bbrc.2004.08.063
Ogawa, D., Stone, J. F., Takata, Y., Blaschke, F., Chu, V. H., Towler, D. A., Law, R. E., Hsueh, W. A. & Bruemmer, D. (2005) Circ. Res. 96, e59-e67.15790955 / Circ. Res. (2005)
10.4049/jimmunol.169.8.4205
10.1093/intimm/dxg113

Dates

Type	When
Created	19 years, 9 months ago (Nov. 14, 2005, 8:33 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 1:51 p.m.)
Indexed	13 hours, 58 minutes ago (Sept. 3, 2025, 6:28 a.m.)
Issued	19 years, 9 months ago (Nov. 14, 2005)
Published	19 years, 9 months ago (Nov. 14, 2005)
Published Online	19 years, 9 months ago (Nov. 14, 2005)
Published Print	19 years, 9 months ago (Nov. 22, 2005)

Funders 0

None

BibTeX

@article{Shinohara_2005, title={T-bet-dependent expression of osteopontin contributes to T cell polarization}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0508666102}, DOI={10.1073/pnas.0508666102}, number={47}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Shinohara, Mari L. and Jansson, Marianne and Hwang, Eun Sook and Werneck, Miriam B. F. and Glimcher, Laurie H. and Cantor, Harvey}, year={2005}, month=nov, pages={17101–17106} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        3
      ]
    ],
    "date-time": "2025-09-03T10:28:36Z",
    "timestamp": 1756895316576
  },
  "reference-count": 29,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "47",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        11,
        22
      ]
    ]
  },
  "abstract": "<jats:p>\n            The osteopontin (Opn) glycoprotein has been implicated in diverse physiological processes, including vascularization, bone formation, and inflammatory responses. Studies of its role in immune responses has suggested that Opn can set the early stage of type-1 immune (cell-mediated) responses through differential regulation of IL-12 and IL-10 cytokine gene expression in macrophages. Although Opn has been suggested to play a role in the development of type-1 immunity, little is known about control of\n            <jats:italic>Opn</jats:italic>\n            gene expression. Here, we report that\n            <jats:italic>Opn</jats:italic>\n            gene expression in activated T cells, but not macrophages, is regulated by T-bet, a transcription factor that controls CD4\n            <jats:sup>+</jats:sup>\n            T helper (Th1) cell lineage commitment. We also find that T-bet-dependent expression of Opn in T cells is essential for efficient skewing of CD4\n            <jats:sup>+</jats:sup>\n            T and CD8\n            <jats:sup>+</jats:sup>\n            T cells toward the Th1 and type 1 CD8\n            <jats:sup>+</jats:sup>\n            T cells (Tc1) pathway, respectively. Taken together, these findings begin to delineate the genetic basis of Opn expression in T cells and further clarify the role of Opn in Th and Tc1 development.\n          </jats:p>",
  "DOI": "10.1073/pnas.0508666102",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        11,
        15
      ]
    ],
    "date-time": "2005-11-15T01:33:40Z",
    "timestamp": 1132018420000
  },
  "page": "17101-17106",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 123,
  "title": "T-bet-dependent expression of osteopontin contributes to T cell polarization",
  "prefix": "10.1073",
  "volume": "102",
  "author": [
    {
      "given": "Mari L.",
      "family": "Shinohara",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Marianne",
      "family": "Jansson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Eun Sook",
      "family": "Hwang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Miriam B. F.",
      "family": "Werneck",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Laurie H.",
      "family": "Glimcher",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Harvey",
      "family": "Cantor",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of Pathology and Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2005,
        11,
        14
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0167-5699(00)01715-1"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI12980"
    },
    {
      "key": "e_1_3_2_3_2",
      "first-page": "578",
      "volume": "126",
      "year": "2001",
      "unstructured": "Weber, G. F. & Cantor, H. (2001) Clin. Exp. Immunol. 126, 578-583.11737079",
      "journal-title": "Clin. Exp. Immunol."
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.287.5454.860"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.79.6.3509-3516.2005"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0002-9440(10)64514-2"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1136/gut.2004.048298"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1062960"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.168.5.2096"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.neuro.25.112701.142913"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI200523273"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/01.ATV.0000074878.29805.D0"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI18141"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood-2004-08-3228"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80702-3"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2636938100"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.1332767100"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.261570598"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ni794"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-1759(02)00424-6"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1074-7613(00)80671-8"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1103336"
    },
    {
      "key": "e_1_3_2_23_2",
      "first-page": "1845",
      "volume": "299",
      "year": "2003",
      "unstructured": "Blom, T., Franzen, A., Heinegard, D. & Holmdahl, R. (2003) Science 299, 1845.12649465",
      "journal-title": "Science"
    },
    {
      "key": "e_1_3_2_24_2",
      "first-page": "H2258",
      "volume": "275",
      "year": "1998",
      "unstructured": "Scott, J. A., Weir, M. L., Wilson, S. M., Xuan, J. W., Chambers, A. F. & McCormack, D. G. (1998) Am. J. Physiol. 275, H2258-H2265.9843827",
      "journal-title": "Am. J. Physiol."
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.70.3.1042-1048.2002"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.bbrc.2004.08.063"
    },
    {
      "key": "e_1_3_2_27_2",
      "first-page": "e59",
      "volume": "96",
      "year": "2005",
      "unstructured": "Ogawa, D., Stone, J. F., Takata, Y., Blaschke, F., Chu, V. H., Towler, D. A., Law, R. E., Hsueh, W. A. & Bruemmer, D. (2005) Circ. Res. 96, e59-e67.15790955",
      "journal-title": "Circ. Res."
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.169.8.4205"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/intimm/dxg113"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0508666102",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T17:51:41Z",
    "timestamp": 1649785901000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0508666102"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        11,
        14
      ]
    ]
  },
  "references-count": 29,
  "journal-issue": {
    "issue": "47",
    "published-print": {
      "date-parts": [
        [
          2005,
          11,
          22
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0508666102"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0508666102",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2005,
        11,
        14
      ]
    ]
  },
  "assertion": [
    {
      "value": "2005-11-14",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}