{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:42:26Z","timestamp":1790890946595,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During hematopoiesis, hematopoietic stem cells constantly differentiate into granulocytes and macrophages via a distinct differentiation program that is tightly controlled by myeloid lineage-specific transcription factors. Mice with a null mutation of IFN regulatory factor 8 (IRF8) accumulate CD11b+Gr1+ myeloid cells that phenotypically and functionally resemble tumor-induced myeloid-derived suppressor cells (MDSCs), indicating an essential role of IRF8 in myeloid cell lineage differentiation. However, IRF8 is expressed in various types of immune cells, and whether IRF8 functions intrinsically or extrinsically in regulation of myeloid cell lineage differentiation is not fully understood. In this study, we report an intriguing finding that, although IRF8-deficient mice exhibit deregulated myeloid cell differentiation and resultant accumulation of CD11b+Gr1+ MDSCs, surprisingly, mice with IRF8 deficiency only in myeloid cells exhibit no abnormal myeloid cell lineage differentiation. Instead, mice with IRF8 deficiency only in T cells exhibited deregulated myeloid cell differentiation and MDSC accumulation. We further demonstrated that IRF8-deficient T cells exhibit elevated GM-CSF expression and secretion. Treatment of mice with GM-CSF increased MDSC accumulation, and adoptive transfer of IRF8-deficient T cells, but not GM-CSF\u2013deficient T cells, increased MDSC accumulation in the recipient chimeric mice. Moreover, overexpression of IRF8 decreased GM-CSF expression in T cells. Our data determine that, in addition to its intrinsic function as an apoptosis regulator in myeloid cells, IRF8 also acts extrinsically to repress GM-CSF expression in T cells to control myeloid cell lineage differentiation, revealing a novel mechanism that the adaptive immune component of the immune system regulates the innate immune cell myelopoiesis in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.1402412","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T06:02:13Z","timestamp":1422943333000},"page":"2369-2379","source":"Crossref","is-referenced-by-count":51,"title":["IFN Regulatory Factor 8 Represses GM-CSF Expression in T Cells To Affect Myeloid Cell Lineage Differentiation"],"prefix":"10.1093","volume":"194","author":[{"given":"Amy V","family":"Paschall","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University , Augusta, GA 30912"},{"name":"Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Georgia Regents University , Augusta, GA 30912"},{"name":"Charlie Norwood VA Medical Center , Augusta, GA 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Feng","family":"Qi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kankana","family":"Bardhan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geming","family":"Lu","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Merad","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"McGaha","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Georgia Regents University , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Georgia Regents University , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mellor","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Georgia Regents University , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott I","family":"Abrams","sequence":"additional","affiliation":[{"name":"Department of Immunology, Roswell Park Cancer Institute , Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Herbert C","family":"Morse","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ozato","sequence":"additional","affiliation":[{"name":"Programs in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kebin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University , Augusta, GA 30912"},{"name":"Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Georgia Regents University , Augusta, GA 30912"},{"name":"Charlie Norwood VA Medical Center , Augusta, GA 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,3,1]]},"reference":[{"key":"2025030705173291200_r1","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.cell.2014.04.016","article-title":"Tissue-specific signals control reversible program of localization and functional polarization of macrophages","volume":"157","author":"Okabe","year":"2014","journal-title":"Cell"},{"key":"2025030705173291200_r2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and 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