{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:41:17Z","timestamp":1790710877934,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,11,11]]},"abstract":"<jats:p>\n                    We have generated mice null for IFN-\u03b2 and report the diverse consequences of IFN-\u03b2 for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor \u03b1 production, relative to IFN-\u03b2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice. Notably, constitutive and induced expression of tumor necrosis factor \u03b1 is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. We also observe an altered splenic architecture in IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, associated with a decrease in B220\n                    <jats:sup>+ve\/high<\/jats:sup>\n                    \/CD43\n                    <jats:sup>-ve<\/jats:sup>\n                    BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the\n                    <jats:italic>in vivo<\/jats:italic>\n                    growth of malignant cells in the IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-\u03b2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-\u03b2 is required during different stages of maturation in the development of the immune system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2230460100","type":"journal-article","created":{"date-parts":[[2003,11,16]],"date-time":"2003-11-16T15:42:47Z","timestamp":1068997367000},"page":"13453-13458","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Critical roles for IFN-\u03b2 in lymphoid development, myelopoiesis, and tumor development: Links to tumor necrosis factor \u03b1"],"prefix":"10.1073","volume":"100","author":[{"given":"Raj","family":"Deonarain","sequence":"first","affiliation":[{"name":"Toronto General Research Institute, University Health Network, Toronto, ON, Canada MG5 2M1; Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8; Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University School of Medicine, Chicago, IL 60611; Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom; and BioLauncher, Cambridge CB4 3PE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Verma","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network, Toronto, ON, Canada MG5 2M1; Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8; Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University School of Medicine, Chicago, IL 60611; Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom; and BioLauncher, Cambridge CB4 3PE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C. G.","family":"Porter","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network, Toronto, ON, Canada MG5 2M1; Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8; Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University School of Medicine, Chicago, IL 60611; Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom; and BioLauncher, Cambridge CB4 3PE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk R.","family":"Gewert","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network, Toronto, ON, Canada MG5 2M1; Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8; Robert H. 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