Inflammation Regulates Haematopoietic Stem Cells and Their Niche

Abstract

Haematopoietic stem cells (HSCs) reside in the bone marrow and are supported by the specialised microenvironment, a niche to maintain HSC quiescence. To deal with haematopoietic equilibrium disrupted during inflammation, HSCs are activated from quiescence directly and indirectly to generate more mature immune cells, especially the myeloid lineage cells. In the process of proliferation and differentiation, HSCs gradually lose their self-renewal potential. The extensive inflammation might cause HSC exhaustion/senescence and malignant transformation. Here, we summarise the current understanding of how HSC functions are maintained, damaged, or exhausted during acute, prolonged, and pathological inflammatory conditions. We also highlight the inflammation-altered HSC niche and its impact on escalating the insults on HSCs.

Inflammation and aging: signaling pathways and intervention therapies

“…18 Numerous pro-inflammatory cytokines and growth factors, including granulocyte colonystimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, IL-3, IL-6, TNF-α, IFNs, and Flt3 ligands, have been found to promote the differentiation of hematopoietic stem/ progenitor cells (HSPCs) towards myeloid cells over lymphoid cells, leading to imbalanced myelopoiesis and lymphopoiesis. [19][20][21] For example, plasma cells that have accumulated in the bone marrow of aged mice can create a feedback loop of pro-inflammatory cytokines, such as IL-1 and TNF-α, which promote HSC myeloid differentiation bias. 22 According to recent studies, bone marrow cells in senescent mice secrete more IL-1α/β, 23 while damaged endosteum produces IL-1β to drive inflammation in the central bone marrow in trans to impede hematopoietic regeneration.…”

The cellular landscape of the endochondral bone during the transition to extrauterine life

“…An attractive hypothesis stemming from our results is that an anti‐inflammatory environment of the perinatal BM could ensure the proper balance between myeloid and lymphoid HSC lineage choice. High pro‐inflammatory conditions promote HSC proliferation and skew their differentiation towards the myeloid lineage at the expense of lymphopoiesis, potentially leading to excessive proliferation and eventual exhaustion of HSC 86 . In addition, and particularly in early life, when individuals are first exposed to pathogens, primary immune organs (bone marrow and thymus) should be protected from infections and the harmful effects of a highly pro‐inflammatory milieu to ensure the establishment of a proper self‐tolerance.…”

The cellular landscape of the endochondral bone during the transition to extrauterine life

“…An attractive hypothesis stemming from our results is that an anti-inflammatory environment of the perinatal bone marrow could ensure the proper balance between myeloid and lymphoid HSC lineage choice. High pro-inflammatory conditions promote HSC division and skew their differentiation towards the myeloid lineage at the expense of lymphopoiesis, potentially leading to excessive proliferation and exhaustion of HSC (Ho and Takizawa, 2022). In addition, and particularly in early life where individuals are first exposed to pathogens, primary immune organs (bone marrow and thymus) should be protected from infections and the deleterious effects of a highly pro-inflammatory milieu, to ensure the establishment of a proper self-tolerance.…”