title: Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
abstract: Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Mark C
authors: MC
authors: Siracusa
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Steven A
authors: SA
authors: Saenz
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Elia D Tait
authors: ED
authors: Wojno
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Brian S
authors: BS
authors: Kim
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Lisa C
authors: LC
authors: Osborne
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Carly G
authors: CG
authors: Ziegler
authors: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Alain J
authors: AJ
authors: Benitez
authors: Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Kathryn R
authors: KR
authors: Ruymann
authors: Department of Surgery and the Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors: Donna L
authors: DL
authors: Farber
authors: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Patrick M
authors: PM
authors: Sleiman
authors: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Hakon
authors: H
authors: Hakonarson
authors: Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Antonella
authors: A
authors: Cianferoni
authors: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Mei-Lun
authors: ML
authors: Wang
authors: Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Jonathan M
authors: JM
authors: Spergel
authors: Inflammation Research, Amgen Inc., Seattle, WA 98119, USA.
authors: Michael R
authors: MR
authors: Comeau
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dartis@mail.med.upenn.edu.
authors: David
authors: D
authors: Artis
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006411:Hematopoiesis, Extramedullary / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D011110:Polymorphism, Genetic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin