Pathomechanisms: homeostatic chemokines in health, tissue regeneration, and progressive diseases

•Homeostatic chemokines support the homing of stem cells and committed progenitor cells. •They also guide immature lymphocytes from bone marrow to thymus and lymph nodes. •Their roles in homeostasis contribute to wound healing and tissue regeneration. •These roles often turn into pathomechanisms, e.g., in chronic inflammation and cancer. Homeostatic chemokines control stem and progenitor cell migration and activation during vasculogenesis and organ development. They orchestrate hematopoietic stem cell (HSC) homing to their bone marrow niches and direct immature lymphocytes to a series of maturation sites within lymphoid organs. Along these lines, homeostatic chemokines regulate the niches of peripheral committed progenitor cell populations for tissue renewal. These biological functions support neovascularization and wound healing, including the recruitment of endothelial and other progenitor cells from the bone marrow. Here, we summarize the roles of homeostatic chemokines, their signaling receptors, and atypical decoy receptors during homeostasis and tissue regeneration in order to better understand their pathogenic roles in disease, for example, in diabetes complications, cancer, autoimmunity, epithelial hyperplasia, or hypertrophic scarring and fibrosis. Homeostatic chemokines control stem and progenitor cell migration and activation during vasculogenesis and organ development. They orchestrate hematopoietic stem cell (HSC) homing to their bone marrow niches and direct immature lymphocytes to a series of maturation sites within lymphoid organs. Along these lines, homeostatic chemokines regulate the niches of peripheral committed progenitor cell populations for tissue renewal. These biological functions support neovascularization and wound healing, including the recruitment of endothelial and other progenitor cells from the bone marrow. Here, we summarize the roles of homeostatic chemokines, their signaling receptors, and atypical decoy receptors during homeostasis and tissue regeneration in order to better understand their pathogenic roles in disease, for example, in diabetes complications, cancer, autoimmunity, epithelial hyperplasia, or hypertrophic scarring and fibrosis. separation of particular cell types or proteins from the blood via an extracorporeal blood circuit and separation device. Stem cell apheresis is needed to harvest HSCs for stem cell transplantation. B lymphocytes, an immune cell subset that is involved in immune responses to extracellular pathogens. cells that secrete CXCL12 to keep HSCs in the bone marrow's perivascular stem cell niche. a cytokine that induces cell migration or homing to a unique site. a lesion within the renal glomerulus characterized by hyperplasia of parietal epithelial cells usually associated with necrotizing glomerulonephritis or other highly inflammatory forms of glomerular inflammation. a bone marrow niche for HSCs along the inner bone surfaces. cells of the bone marrow that can enter the circulation and generate new endothelial cells within the vasculature where needed, for example, during angiogenesis and vasculogenesis. cells of the immune system that are involved in host defense as well as in allergic diseases. a bone marrow-derived cell that coexpresses monocyte markers and collagen I, and recruits to sites of injury to produce collagen and to promote fibrosis. γ-aminobutyric acid is a neurotransmitter that regulates neuronal excitability. a subgroup of the homeostatic chemokines that were first described in filtration fluid obtained from patients on hemodialysis for end-stage renal disease. stem cells that serve as blood cell precursors. tissue suffering from oxygen depletion, which impairs energy metabolism. cells of the immune system that also include the white blood cells. the step-wise maturation of lymphocytes from their bone marrow precursors, which takes place in the thymus and other lymphoid organs. Directed migration of the immature cells is needed for this process. a stromal cell of the bone marrow that supports the HSC niches. The MSC of the vascular niche is also called ‘CXCL12 abundant reticular (CAR)’ cell. MSC can enter the circulation and contribute to renewal, regeneration, and repair of tissue injuries. blood cells that serve as precursors for tissue macrophages, as a subtype of the mononuclear phagocytes that serve multiple functions in particle clearance, inflammation, and wound healing. monocytic phagocytes and granulocytes that develop from bone marrow precursors. the step-wise differentiation of mononuclear phagocytes and granulocytes in bone marrow from their common stem cells and lineage-specific precursors. a significant drop in the number of circulating neutrophils, which, in most cases, is due to an insufficient production and mobilization of neutrophils from the bone marrow. a particular site and microenvironment that allows stem cells to rest in quiescence or to undergo proliferation and differentiation. a mechanism that promotes the onset and progression of disease. For example, the regulation of our immune system should generate maximal host defense at a minimum of tissue damage, but either insufficient immunity (immunodeficiency) or overshooting inflammation (e.g., fatal cytokine storm in early sepsis) cause disease. In autoinflammatory and autoimmune disorders, as well as in all forms of sterile and/or chronic inflammation, it becomes obvious that host defense turns into inappropriate immunopathology, i.e., a pathomechanism. an epithelial cell of the renal glomerulus. Its sophisticated anatomical structure is an important element of the glomerular filtration barrier. an immature cell that is committed to differentiate into cells of a particular lineage. Its capacity to proliferate declines with differentiation. the replacement of tissue cells that are lost due to physiological turnover. the replacement of tissue cells that are lost during injury. a resting state of G0 stem cells, implies resistance to cell cycle toxins. incomplete replacement of tissue cells that get lost during injury, often associated with some degree of tissue atrophy and scarring. sites of lymphocyte maturation and antigen presentation including spleen, lymph nodes, tonsils, and other mucosa-associated lymphoid tissues. a cell with the potential for self-renewal, for example, by asymmetric division, and the capacity to differentiate into progeny with specific functional properties. the ability to self-renew and to generate differentiated progeny. T lymphocytes, an immune cell subset that is involved in host defense against intracellular pathogens; certain T cell subtypes have additional immunoregulatory functions. the spectrum of T cell receptor specificities that persists after negative selection and is ready to detect and respond to non-self (and self) antigens. de novo lymphoid tissue formation that can develop at sites of chronic inflammation. This process is induced by lymphoid inducer cells that produce lymphotoxin-α, which induces local production of homeostatic chemokines that recruit lymphocytes, antigen-presenting cells, and endothelial progenitor cells. immune cells that undergo maturation steps while passing through the thymus. the bone marrow stem cell niche around vessels that connect the bone marrow with the vasculature of the peripheral circulation.