Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation

  • Immunity. 2013 Dec 12;39(6):1158-70. doi: 10.1016/j.immuni.2013.09.016.
Mark C Siracusa  1 ,  Steven A Saenz  1 ,  Elia D Tait Wojno  1 ,  Brian S Kim  2 ,  Lisa C Osborne  1 ,  Carly G Ziegler  1 ,  Alain J Benitez  3 ,  Kathryn R Ruymann  4 ,  Donna L Farber  5 ,  Patrick M Sleiman  6 ,  Hakon Hakonarson  6 ,  Antonella Cianferoni  4 ,  Mei-Lun Wang  3 ,  Jonathan M Spergel  4 ,  Michael R Comeau  7 ,  David Artis  8
Affiliations
  • 1. Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 2. 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.
  • 3. Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 4. Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 5. Department of Surgery and the Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
  • 6. 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.
  • 7. Inflammation Research, Amgen Inc., Seattle, WA 98119, USA.
  • 8. 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: [email protected].
PMID: 24332033 DOI: 10.1016/j.immuni.2013.09.016
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.

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