Hematopoietic stem cells and progenitors (HSPCs) have long been considered mostly as the indispensable reservoir, confined within the bone marrow, for continuous replenishment of all cells in the blood and the immune system. However, emerging evidence suggests that beyond this principal role, HSPCs can integrate inflammatory signals and influence the outcome of immune responses. For instance, HSPCs express a number of receptors for innate signals, which upon activation promote HSPC trafficking through peripheral tissues. Within sites of active immune responses HSPCs interact with mature immune cells. Nonetheless, whether HSPCs may exert either an immune-enhancing effect or, conversely, an immunoregulatory effect on initiating or ongoing immune responses remains a relevant yet unanswered question.
Of major importance, recent data suggest that inflammatory conditions can lead to a type of unspecific, innate memory, termed trained immunity, which is already imprinted at the level of HSPCs. Indeed, direct innate activation switches HSC differentiation towards the myeloid lineages, leading to the generation of monocytes and macrophages, which present a primed state of hyper-responsiveness that enhances their innate immune function upon subsequent challenge.
Conversely, manipulation of HSPCs, through a variety of innate signals and pharmacological treatments, has been shown to confer immunoregulatory properties to HSPCs, which may then be instrumental in the control of immune responses. Of interest, enhancing the therapeutic aspects of HSPCs is now possible through the use of high-throughput screening strategies and may, therefore, support their potential use in the treatment of autoimmune diseases and may portend to elaborate a safer therapy while minimizing/eliminating the toxic conditioning. HSPCs have successfully rendered patients suffering from autoimmune diseases, disease-free. The aim behind the use of HSPCs is the overall resetting/conversion of an aberrant autoreactive immune system to a de novo self-tolerant immune system. HSCPs may exert their immunoregulatory functions at the multipotent stage of differentiation but also after differentiation into lineage-specific progenitors. These immunoregulatory effects may arise directly, through the in vivo differentiation into mature cells with regulatory properties, as well as from the capacity of HSPCs to stimulate the expansion and suppressive activity of regulatory cell subsets, such as Foxp3 Tregs which might efficiently eliminate autoreactive T cells. Finally, HSPCs and mature cell derivatives have been proposed to participate in the control of HSC maintenance, either directly or via the remodeling of HSC niche components.
The aim of this Research Topic is to gather novel Original Research and Review articles focusing on the various conditions that confer HSPCs the capacity to modulate immune responses and explore the cellular and molecular mechanisms that underline these properties. We welcome contributions focusing on, but not limited to, the following subtopics:
1. HSPCs memory formation
2. HSPCs immunoregulatory functions
3. HSPCs immune-enhancing functions
4. HSPCs control of BM HSC niches
5. HSPCs use in clinical trials for autoimmune diseases
Hematopoietic stem cells and progenitors (HSPCs) have long been considered mostly as the indispensable reservoir, confined within the bone marrow, for continuous replenishment of all cells in the blood and the immune system. However, emerging evidence suggests that beyond this principal role, HSPCs can integrate inflammatory signals and influence the outcome of immune responses. For instance, HSPCs express a number of receptors for innate signals, which upon activation promote HSPC trafficking through peripheral tissues. Within sites of active immune responses HSPCs interact with mature immune cells. Nonetheless, whether HSPCs may exert either an immune-enhancing effect or, conversely, an immunoregulatory effect on initiating or ongoing immune responses remains a relevant yet unanswered question.
Of major importance, recent data suggest that inflammatory conditions can lead to a type of unspecific, innate memory, termed trained immunity, which is already imprinted at the level of HSPCs. Indeed, direct innate activation switches HSC differentiation towards the myeloid lineages, leading to the generation of monocytes and macrophages, which present a primed state of hyper-responsiveness that enhances their innate immune function upon subsequent challenge.
Conversely, manipulation of HSPCs, through a variety of innate signals and pharmacological treatments, has been shown to confer immunoregulatory properties to HSPCs, which may then be instrumental in the control of immune responses. Of interest, enhancing the therapeutic aspects of HSPCs is now possible through the use of high-throughput screening strategies and may, therefore, support their potential use in the treatment of autoimmune diseases and may portend to elaborate a safer therapy while minimizing/eliminating the toxic conditioning. HSPCs have successfully rendered patients suffering from autoimmune diseases, disease-free. The aim behind the use of HSPCs is the overall resetting/conversion of an aberrant autoreactive immune system to a de novo self-tolerant immune system. HSCPs may exert their immunoregulatory functions at the multipotent stage of differentiation but also after differentiation into lineage-specific progenitors. These immunoregulatory effects may arise directly, through the in vivo differentiation into mature cells with regulatory properties, as well as from the capacity of HSPCs to stimulate the expansion and suppressive activity of regulatory cell subsets, such as Foxp3 Tregs which might efficiently eliminate autoreactive T cells. Finally, HSPCs and mature cell derivatives have been proposed to participate in the control of HSC maintenance, either directly or via the remodeling of HSC niche components.
The aim of this Research Topic is to gather novel Original Research and Review articles focusing on the various conditions that confer HSPCs the capacity to modulate immune responses and explore the cellular and molecular mechanisms that underline these properties. We welcome contributions focusing on, but not limited to, the following subtopics:
1. HSPCs memory formation
2. HSPCs immunoregulatory functions
3. HSPCs immune-enhancing functions
4. HSPCs control of BM HSC niches
5. HSPCs use in clinical trials for autoimmune diseases
