title: Cutting edge: Type I IFN drives emergency myelopoiesis and peripheral myeloid expansion during chronic TLR7 signaling.
abstract: Mice overexpressing TLR7 (TLR7.1 mice) are a model of systemic lupus erythematosus pathogenesis and exhibit peripheral myeloid expansion. We show that TLR7.1 mice have a dramatic expansion of splenic cells that derive from granulocyte/macrophage progenitors (GMP) compared with wild-type mice. In the bone marrow, TLR7.1 mice exhibited hallmarks of emergency myelopoiesis and contained a discrete population of Sca-1(+) GMP, termed emergency GMP, which are more proliferative and superior myeloid precursors than classical Sca-1(-) GMP. The emergency myelopoiesis and peripheral myeloid expansion in TLR7.1 mice was dependent on type I IFN signaling. TLR7 agonist administration to nontransgenic mice also drove type I IFN-dependent emergency myelopoiesis. TLR7.1 plasmacytoid dendritic cells were cell-intrinsically activated by TLR7 overexpression and constitutively produced type I IFN mRNA. This study shows that type I IFN can act upon myeloid progenitors to promote the development of emergency GMP, which leads to an expansion of their progeny in the periphery.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Buechler
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Teal
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hamerman
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D006098:Granulocytes / Q000473:pathology; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D022423:Myeloid Cells / Q000473:pathology; D038042:Myelopoiesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011828:Radiation Chimera; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; C074650:Ly6a protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D053633:Receptor, Interferon alpha-beta