Journal Article

IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion

Hunter, Christopher A, Pardy, Ryan D, Lanzar, Zachary, Aldridge, Daniel L, Christian, David A, Min, Booki, Phan, Anthony T, Kedl, Ross

2025

Overview

Many inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with trained immunity and have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected with Toxoplasma gondii , there was enhanced generation of monocyte progenitors and increased numbers of inflammatory monocytes. In the bone marrow of infected mice, there was increased production of IL-27 that localized with HSPCs, and a survey of cytokine receptor expression highlighted that HSPCs were uniquely poised to respond to IL-27. Furthermore, the use of in vitro differentiation assays and mixed bone marrow chimeras revealed that HSPCs from IL-27-deficient mice are predisposed toward the monocyte lineage. Additional studies highlighted that after infection, loss of the IL-27R resulted in reduced HSPC fitness that manifested as reduced proliferative responses and a decreased ability to reconstitute the hematopoietic system. Thus, the ability of IL-27 to act on HSPC provides a regulatory brake on differentiation to limit monocyte induction and preserve HSPC stemness.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Animals / anti-inflammatory agents / B cells / Bone marrow / Cell Differentiation / Chimeras / Cytokines / Dendritic cells / Epigenetics / Granulocytes / haematopetic stem cells / Health aspects / Hematopoietic stem cells / Hematopoietic Stem Cells - physiology / Hemopoiesis / host-defense system / IL-27 / Immunology and Inflammation / Infection control / Infections / Inflammation / Interleukin 27 / Interleukin-27 - genetics / Interleukin-27 - metabolism / Interleukins - metabolism / Medical research / Medicine, Experimental / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / Monocytes / Myeloid cells / Myelopoiesis / Neutrophils / Osteoprogenitor cells / Progenitor cells / Spleen / Stem cells / Stem Cells and Regenerative Medicine / Toxoplasma / toxoplasmosis / Toxoplasmosis - immunology