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[Untitled]

Authors :
Lisa C. Osborne
Steven A. Saenz
Patrick M. A. Sleiman
Donna L. Farber
Elia D. Tait Wojno
Mark C. Siracusa
David Artis
Jonathan M. Spergel
Michael R. Comeau
Brian S. Kim
Mei-Lun Wang
Alain Benitez
Hakon Hakonarson
Antonella Cianferoni
Kathryn Ruymann
Source :
Cytokine. 63:301
Publication Year :
2013
Publisher :
Elsevier BV, 2013.

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 established a link between pattern recognition receptor-expressing HSCs, EMH and innate immune responses to bacterial or viral pathogens. However, the factors that regulate EMH and whether EMH is a conserved mechanism of innate immunity to diverse stimuli remain poorly defined. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of Lineage − , CD34 + , c-Kit + granulocyte-monocyte progenitor (GMP)-like cells in the periphery. TSLP-elicited progenitors possess the capacity to differentiate into macrophages, mast cells and basophils. Critically, adoptive transfer of TSLP-elicited GMP-like cells was sufficient to promote Th2 cytokine-dependent immunity to an intestinal helminth parasite, demonstrating a role for TSLP-elicited GMP-like cells in promoting inflammation. Further, circulating progenitor cells were also increased in allergic patients with a gain-of-function polymorphism in TSLP , suggesting that the TSLP-EMH pathway may be operational in human disease. These data demonstrate a previously unrecognized role for TSLP in promoting EMH that contributes to the development of Th2-cytokine-mediated inflammation and identify the TSLP-EMH pathway as a possible therapeutic target to treat allergic inflammation.

Details

ISSN :
10434666
Volume :
63
Database :
OpenAIRE
Journal :
Cytokine
Accession number :
edsair.doi...........7bf954df820c51a34d414bdb08782b47