246 : TSLP-mediated extramedullary hematopoiesis promotes allergic inflammation

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• 作者：Mark C. Siracusa ; Elia D. Tait Wojno ; Lisa C. Osborne ; Steven A. Saenz ; Brian S. Kim ; Alain J. Benitez ; Kathryn R. Ruymann ; Donna L. Farber ; Patrick M. Sleiman ; Hakon Hakonarson ; Antonella Cianferoni ; Mei-Lun Wang ; Jonathan M. Spergel ; Michael R. Comeau ; David Artis
• 刊名：Cytokine
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：63
• 期：3
• 页码：301
• 全文大小：42 K

文摘

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.