Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis.
Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated to play a critical role in the expansion...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-03-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC4798290?pdf=render |
id |
doaj-41531e25bff24e9b86055af1a9c18573 |
---|---|
record_format |
Article |
spelling |
doaj-41531e25bff24e9b86055af1a9c185732020-11-24T22:09:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-03-01123e100550710.1371/journal.ppat.1005507Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis.Jun-ichi FurusawaIzuru MizoguchiYukino ChibaMasayuki HisadaFumie KobayashiHiroki YoshidaSusumu NakaeAkihiko TsuchidaTetsuya MatsumotoHideo EmaJunichiro MizuguchiTakayuki YoshimotoEmergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated to play a critical role in the expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, leading to production of mature myeloid cells, although their inhibitory effects on hematopoiesis were also reported. Therefore, the molecular mechanism of emergency myelopoiesis during infection remains incompletely understood. Here, we clarify that one of the interleukin (IL)-6/IL-12 family cytokines, IL-27, plays an important role in the emergency myelopoiesis. Among various types of hematopoietic cells in bone marrow, IL-27 predominantly and continuously promoted the expansion of only Lineage-Sca-1+c-Kit+ (LSK) cells, especially long-term repopulating HSCs and myeloid-restricted progenitor cells with long-term repopulating activity, and the differentiation into myeloid progenitors in synergy with stem cell factor. These progenitors expressed myeloid transcription factors such as Spi1, Gfi1, and Cebpa/b through activation of signal transducer and activator of transcription 1 and 3, and had enhanced potential to differentiate into migratory dendritic cells (DCs), neutrophils, and mast cells, and less so into macrophages, and basophils, but not into plasmacytoid DCs, conventional DCs, T cells, and B cells. Among various cytokines, IL-27 in synergy with the stem cell factor had the strongest ability to augment the expansion of LSK cells and their differentiation into myeloid progenitors retaining the LSK phenotype over a long period of time. The experiments using mice deficient for one of IL-27 receptor subunits, WSX-1, and IFN-γ revealed that the blood stage of malaria infection enhanced IL-27 expression through IFN-γ production, and the IL-27 then promoted the expansion of LSK cells, differentiating and mobilizing them into spleen, resulting in enhanced production of neutrophils to control the infection. Thus, IL-27 is one of the limited unique cytokines directly acting on HSCs to promote differentiation into myeloid progenitors during emergency myelopoiesis.http://europepmc.org/articles/PMC4798290?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun-ichi Furusawa Izuru Mizoguchi Yukino Chiba Masayuki Hisada Fumie Kobayashi Hiroki Yoshida Susumu Nakae Akihiko Tsuchida Tetsuya Matsumoto Hideo Ema Junichiro Mizuguchi Takayuki Yoshimoto |
spellingShingle |
Jun-ichi Furusawa Izuru Mizoguchi Yukino Chiba Masayuki Hisada Fumie Kobayashi Hiroki Yoshida Susumu Nakae Akihiko Tsuchida Tetsuya Matsumoto Hideo Ema Junichiro Mizuguchi Takayuki Yoshimoto Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. PLoS Pathogens |
author_facet |
Jun-ichi Furusawa Izuru Mizoguchi Yukino Chiba Masayuki Hisada Fumie Kobayashi Hiroki Yoshida Susumu Nakae Akihiko Tsuchida Tetsuya Matsumoto Hideo Ema Junichiro Mizuguchi Takayuki Yoshimoto |
author_sort |
Jun-ichi Furusawa |
title |
Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. |
title_short |
Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. |
title_full |
Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. |
title_fullStr |
Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. |
title_full_unstemmed |
Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. |
title_sort |
promotion of expansion and differentiation of hematopoietic stem cells by interleukin-27 into myeloid progenitors to control infection in emergency myelopoiesis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2016-03-01 |
description |
Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated to play a critical role in the expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, leading to production of mature myeloid cells, although their inhibitory effects on hematopoiesis were also reported. Therefore, the molecular mechanism of emergency myelopoiesis during infection remains incompletely understood. Here, we clarify that one of the interleukin (IL)-6/IL-12 family cytokines, IL-27, plays an important role in the emergency myelopoiesis. Among various types of hematopoietic cells in bone marrow, IL-27 predominantly and continuously promoted the expansion of only Lineage-Sca-1+c-Kit+ (LSK) cells, especially long-term repopulating HSCs and myeloid-restricted progenitor cells with long-term repopulating activity, and the differentiation into myeloid progenitors in synergy with stem cell factor. These progenitors expressed myeloid transcription factors such as Spi1, Gfi1, and Cebpa/b through activation of signal transducer and activator of transcription 1 and 3, and had enhanced potential to differentiate into migratory dendritic cells (DCs), neutrophils, and mast cells, and less so into macrophages, and basophils, but not into plasmacytoid DCs, conventional DCs, T cells, and B cells. Among various cytokines, IL-27 in synergy with the stem cell factor had the strongest ability to augment the expansion of LSK cells and their differentiation into myeloid progenitors retaining the LSK phenotype over a long period of time. The experiments using mice deficient for one of IL-27 receptor subunits, WSX-1, and IFN-γ revealed that the blood stage of malaria infection enhanced IL-27 expression through IFN-γ production, and the IL-27 then promoted the expansion of LSK cells, differentiating and mobilizing them into spleen, resulting in enhanced production of neutrophils to control the infection. Thus, IL-27 is one of the limited unique cytokines directly acting on HSCs to promote differentiation into myeloid progenitors during emergency myelopoiesis. |
url |
http://europepmc.org/articles/PMC4798290?pdf=render |
work_keys_str_mv |
AT junichifurusawa promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT izurumizoguchi promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT yukinochiba promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT masayukihisada promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT fumiekobayashi promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT hirokiyoshida promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT susumunakae promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT akihikotsuchida promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT tetsuyamatsumoto promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT hideoema promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT junichiromizuguchi promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis AT takayukiyoshimoto promotionofexpansionanddifferentiationofhematopoieticstemcellsbyinterleukin27intomyeloidprogenitorstocontrolinfectioninemergencymyelopoiesis |
_version_ |
1725813342831902720 |