Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.

TitleThymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Publication TypeJournal Article
Year of Publication2013
AuthorsSiracusa MC, Saenz SA, Wojno EDTait, Kim BS, Osborne LC, Ziegler CG, Benitez AJ, Ruymann KR, Farber DL, Sleiman PM, Hakonarson H, Cianferoni A, Wang M-L, Spergel JM, Comeau MR, Artis D
JournalImmunity
Volume39
Issue6
Pagination1158-70
Date Published2013 Dec 12
ISSN1097-4180
KeywordsAnimals, Cytokines, Disease Models, Animal, Flow Cytometry, Gene Expression Profiling, Hematopoiesis, Extramedullary, Humans, Hypersensitivity, Inflammation, Mice, Mice, Inbred C57BL, Polymorphism, Genetic, Precursor Cells, B-Lymphoid, Spleen, Trichinellosis
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.

DOI10.1016/j.immuni.2013.09.016
Alternate JournalImmunity
PubMed ID24332033
PubMed Central IDPMC3959827
Grant ListAI061570 / AI / NIAID NIH HHS / United States
AI06697 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI083480 / AI / NIAID NIH HHS / United States
AI085828 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
AI097333 / AI / NIAID NIH HHS / United States
AI102942 / AI / NIAID NIH HHS / United States
KL2-RR024132 / RR / NCRR NIH HHS / United States
KL2TR000139 / TR / NCATS NIH HHS / United States
P01 AI106697 / AI / NIAID NIH HHS / United States
P30 AR057217 / AR / NIAMS NIH HHS / United States
P30 CA016520 / CA / NCI NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI074878 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI097333 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
R01 DK087789 / DK / NIDDK NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States

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