The Role of Extra-Cellular Signals in Hematopoiesis

Dear colleagues,

The outstanding ability of the immune system to provide efficient and life-long protection against an enormous variety of pathogens is based on two hallmark properties of immune cells: their continuous regeneration from hematopoietic stem cells (hematopoiesis) and their capacity to rapidly modify several of their attributes, such as differentiation potential, cell cycle, activation state or metabolism in response to particular pathogenic insults. Both these properties are regulated by extra-cellular signals produced by the microenvironment in which immune cells reside. Cytokines, chemokines, extra-cellular matrix proteins and cell membrane-bound ligands represent the most common types of extra-cellular regulators of immune cell development and activation. The steady-state differentiation of hematopoietic stem and progenitor cells into the various immune cell types is under the control of such regulators, with cytokines being the most prominent amongst them. Moreover, it is becoming increasingly evident that inflammation and chronic infections can modify hematopoietic development, ensuring that the immune cell output adapts to the demand at hand, thus underscoring the dynamic nature of hematopoiesis. Inflammatory cytokines are central mediators of this adaptation of the hematopoietic system to emergency situations. Recent evidence suggests that apart from infections, vaccination can also shape hematopoiesis, thus introducing the concept of “trained immunity”. Even though the mechanisms by which this occurs are currently under investigation, it is clear that extra-cellular signals are key players in the “training” of innate immune cells and progenitors.

This central role of extra-cellular cues in the regulation of both steady-state and emergency hematopoiesis calls for a better understanding of their precise function, with the aim not only to further elucidate the biology of immune cell development and function, but also to assess the potential therapeutic use of this knowledge in pathological situations. In this special issue we welcome research findings, methodologies and reviews that provide insights into the mechanisms by which extra-cellular signals and the intra-cellular pathways they activate regulate hematopoiesis.

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• hematopoiesis
• hematopoietic stem cells
• cytokines
• inflammation
• interleukins
• emergency hematopoiesis
• trained immunity
• lineage commitment
• cytokine signaling
• hematopoietic niche