Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases
Joseph Cannova1,2,Peter Breslin S.J.3,5,6,*(),Jiwang Zhang1,3,4,*()
1. Biochemistry and Molecular Biology Program, Loyola University Chicago, Maywood, IL 60153, USA 2. Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA 3. Oncology Institute, Loyola University Chicago, Maywood, IL 60153, USA 4. Department of Pathology, Loyola University Chicago, Maywood, IL 60153, USA 5. Department of Biology, Loyola University Chicago, Chicago, IL 60660, USA 6. Department of Molecular and Cellular Physiology, Loyola University Chicago, Maywood, IL 60153, USA
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.
Corresponding Author(s):
Peter Breslin S.J.,Jiwang Zhang
引用本文:
. [J]. Frontiers of Medicine, 2015, 9(3): 288-303.
Joseph Cannova,Peter Breslin S.J.,Jiwang Zhang. Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases. Front. Med., 2015, 9(3): 288-303.
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