Cellular and Molecular Life Sciences

, Volume 75, Issue 8, pp 1363–1376 | Cite as

Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases

  • Yukino Chiba
  • Izuru Mizoguchi
  • Hideaki Hasegawa
  • Mio Ohashi
  • Naoko Orii
  • Taro Nagai
  • Miyaka Sugahara
  • Yasunori Miyamoto
  • Mingli Xu
  • Toshiyuki Owaki
  • Takayuki Yoshimoto


Hematopoiesis is hierarchically orchestrated by a very small population of hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are tightly regulated to maintain homeostatic blood production. HSCs are predominantly quiescent, but they enter the cell cycle in response to inflammatory signals evoked by severe systemic infection or injury. Thus, hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen recognition receptors and proinflammatory cytokines to induce emergency myelopoiesis during infection. This emergency myelopoiesis counterbalances the loss of cells and generates lineage-restricted hematopoietic progenitors, eventually replenishing mature myeloid cells to control the infection. Controlled generation of such signals effectively augments host defense, but dysregulated stimulation by these signals is harmful to HSPCs. Such hematopoietic failure often results in blood disorders including chronic inflammatory diseases and hematological malignancies. Recently, we found that interleukin (IL)-27, one of the IL-6/IL-12 family cytokines, has a unique ability to directly act on HSCs and promote their expansion and differentiation into myeloid progenitors. This process resulted in enhanced production of neutrophils by emergency myelopoiesis during the blood-stage mouse malaria infection. In this review, we summarize recent advances in the regulation of myelopoiesis by proinflammatory cytokines including type I and II interferons, IL-6, IL-27, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in infectious diseases.


Hematopoietic stem cell Hematopoietic progenitor cell Cytokine Emergency myelopoiesis 



Bone marrow


C-X-C motif ligand 12-abundant reticular


Cytotoxic CD8+ T cell


C-X-C motif ligand


Dendritic cell


Endothelial cell


Granulocyte colony-stimulating factor


β-Receptor glycoprotein 130


Granulocyte macrophage colony-stimulating factor


Hematopoietic stem cell


Hematopoietic stem and progenitor cell




IFN-α receptor




Janus kinase


Lymphocytic choriomeningitis virus




Long-term repopulating hematopoietic stem cell


Macrophage colony-stimulating factor


Myeloid-derived suppressor cell


Multipotent progenitor


Myeloid differentiation primary response gene 88


Myeloid-restricted progenitor cell


Mesenchymal stem/stromal cell


Natural killer






Red blood cell


Stem cell antigen-1


Stem cell factor


Signal transducer and activator of transcription


Helper T


Toll-like receptor


Regulatory T



This study was supported in part by a Grant-in-aid and the Private University Strategic Research Based Support Project from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Yukino Chiba
    • 1
  • Izuru Mizoguchi
    • 1
  • Hideaki Hasegawa
    • 1
  • Mio Ohashi
    • 1
  • Naoko Orii
    • 1
  • Taro Nagai
    • 2
  • Miyaka Sugahara
    • 1
    • 3
  • Yasunori Miyamoto
    • 3
  • Mingli Xu
    • 1
  • Toshiyuki Owaki
    • 1
  • Takayuki Yoshimoto
    • 1
  1. 1.Department of ImmunoregulationInstitute of Medical Science, Tokyo Medical UniversityTokyoJapan
  2. 2.Department of ImmunologyTokyo Medical UniversityTokyoJapan
  3. 3.Institute for Human Life Innovation, Ochanomizu UniversityTokyoJapan

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