title: Monocyte/macrophage lineage commitment and distribution are affected by the lack of regulatory T cells in scurfy mice.
abstract: Foxp3(+) regulatory T (Treg) cells play a pivotal role in maintaining immunological tolerance. Loss-of-function mutations in the Foxp3 gene result in multiorgan inflammation known as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in humans and scurfy (Sf) disease in mice. While the impact of missing Treg cells on adaptive immune cells is well documented, their role in regulation of myeloid cells remains unclear. Here we report that Sf mice exhibit an altered composition of stem and progenitor cells, characterized by increased numbers of myeloid precursors and higher efficiency of macrophage generation ex vivo. The proportion of monocytes/macrophages in the bone marrow, blood, and spleen was significantly elevated in Sf mice, which was accompanied with tissue-specific monocyte expression of homing receptor and phagocytic activity. Sf mice displayed high levels of M-CSF and other inflammatory cytokines, including monocyte-recruiting chemokines. Adoptive transfer of WT CD4(+) cells and in vivo neutralization of M-CSF normalized frequencies of monocyte subsets and their progenitors and reduced high levels of monocyte-related cytokines in Sf mice, while Treg cell transfer to RAG2(-/-) mice had no effect on myelopoiesis and monocyte/macrophage counts. Our findings illustrate that deregulated myelopoiesis in Sf mice is mainly caused by the inflammatory reaction resulting from the lack of Treg cells.
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Skuljec
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Maciej
authors.initials: M
authors.lastname: Cabanski
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Ewa
authors.initials: E
authors.lastname: Surdziel
authors.affiliation: Reprogramming and Gene Therapy Group, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.|Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Lachmann
authors.affiliation: Reprogramming and Gene Therapy Group, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.|Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brennig
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Refik
authors.initials: R
authors.lastname: Pul
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Adan C
authors.initials: AC
authors.lastname: Jirmo
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Habener
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Visic
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Dalüge
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hennig
authors.affiliation: Reprogramming and Gene Therapy Group, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.|Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Happle
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000172:deficiency*; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D016173:Macrophage Colony-Stimulating Factor
keywords: Foxp3; Inflammation; Macrophages; Monocytes; Myelopoiesis; Regulatory T cells; Scurfy mice