Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

• Published in: Experimental cell research Vol. 329; no. 2; pp. 239 - 247
• Main Authors: Libregts, Sten F.W.M., Nolte, Martijn A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-12-2014; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Blood; BLOOD CELLS; BLOOD FORMATION; BONE MARROW; Bone Marrow - immunology; Bone Marrow - metabolism; Cell Differentiation - immunology; CELL PROLIFERATION; Cellular biology; Co-stimulation; Cytokines; Hematopoiesis; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; HSC; Humans; Immune activation; Immune system; INFLAMMATION; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Lymphocyte Activation - immunology; Lymphocytes; LYMPHOKINES; PATHOGENS; SIGNALS; STEM CELLS; Stress, Physiological; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TLRs; HSC; Immune activation; Co-stimulation; Cytokines; Hematopoiesis; TLRs
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2014.09.016

Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection.
•Inflammation and infection have a direct impact on hematopoiesis in the bone marrow.•We draw a striking parallel between immune-driven hematopoiesis and T cell activation.•We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.