Gene expression profiling of nave bone marrow-resident granulocyte monocyte precursors (GMPs) and TSLP-elicited splenic GMP-like cells

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, the factors that regulate EMH and whether EMH operates in broader immune contexts remain 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 differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 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 may 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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Siracusa MC, Saenz SA, Wojno ED, Kim BS, Osborne LC, Ziegler CG, Benitez AJ, Ruymann KR, Farber DL, Sleiman PM, Hakonarson H, Cianferoni A, Wang ML, Spergel JM, Comeau MR, Artis D