title: Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases.
abstract: Toll-like receptors (TLRs), which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self-renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.
authors: Biochemistry and Molecular Biology Program, Loyola University Chicago, Maywood, IL, 60153, USA.
authors: Joseph
authors: J
authors: Cannova
authors: Peter
authors: P
authors: Breslin S J
authors: Jiwang
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors