Research Topic

Inflammatory signaling in bone marrow failure and hematopoietic malignancy

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The inflammatory response to cellular damage or pathogen exposure is a complex and tightly regulated process involving a diverse array of hematopoietic effector immune cells and inflammatory cytokines. While the role of committed effector cells in the inflammatory response has long been appreciated, ...

The inflammatory response to cellular damage or pathogen exposure is a complex and tightly regulated process involving a diverse array of hematopoietic effector immune cells and inflammatory cytokines. While the role of committed effector cells in the inflammatory response has long been appreciated, accumulating reports demonstrate that inflammatory stimuli influence hematopoiesis from the level of the stem and progenitor cells. Hematopoietic stem and progenitor cells (HSPCs), which give rise to all of the effector immune cells in the blood, express receptors for inflammatory cytokines (eg, IFN, TNF) and even pathogens themselves (eg, TLRs). Exposure to these signals promotes HSPC cycling and influences their differentiation potential, which, in the short term, may optimize the production and mobilization of effector cells for elimination of an offending stimulus. Chronic or aberrant exposure to inflammatory signals, however, often leads to a loss of HSPC function, and is associated with bone marrow failure and malignancy. For example, enhanced toll like receptor (TLR) signaling is associated with myelodysplastic syndrome (MDS), a hematopoietic stem cell disorder characterized by ineffective hematopoiesis and a high risk of transformation to acute leukemia.

In this Frontiers topic, we will explore the relationship between inflammatory signals and bone marrow failure and hematopoietic malignancy, focusing on the mechanisms by which such signals may influence HSPCs and contribute to their loss of function and malignant transformation.

Specific topics addressed might include (but are not limited to):

-Toll like receptor signaling in myelodysplastic syndrome
-Toll like receptor signaling in lymphoproliferative disease
-Role of inflammatory cytokines in the pathogenesis of bone marrow failure
-Regulation of hematopoietic stem and progenitor cells by pattern recognition receptors and inflammatory cytokines
-Effects of inflammatory signals on bone marrow stromal cells


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