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37Īll antibodies were purchased from eBiosciences or BioLegend, unless stated otherwise. 34-36, 38 TLR activation of circulating HSPCs was further suggested to induce a migratory arrest and differentiation at sites of inflammation. Recent studies suggest that direct sensing of TLR agonists by HSPCs may skew their lineage differentiation toward myeloid cells and DCs. 36 Although the effects of TLR triggering on mature cells are well defined, little is known about the biologic relevance of TLR expression on HSPCs. 38 In fact, systemically injected lipopolysaccharide (LPS) binds to TLR4 on HSPCs in the BM. Once pathogens spread from a local site of infection to the blood, they can act directly on BM cells. 32 Recent studies indicate that human 33-35 and mouse HSPCs 36-38 express TLRs. 31 TLR triggering leads to cell activation and production of inflammatory cytokines. 31 Toll-like receptors (TLRs) are pattern-recognition receptors that are integrated into cellular membranes and detect exogenous pathogens. Immune and stroma cells sense pathogen-associated molecular patterns (PAMPs) of invading microbes via pattern-recognition receptors. This mechanism likely developed to support DC homeostasis on specific need at sites of inflammation. Consequently, BM DC progenitors can sense TLR agonists and, via regulation of CXCR4 and CCR7, support the replenishment of DCs in reactive LNs. When TLR agonists were injected locally, CDPs preferentially gave rise to DCs in inflamed LNs in expense of noninflamed LNs and the BM, but they did not alter their lineage differentiation and proliferative activity. On TLR stimulation, CDPs down-regulated CXCR4, the nonredundant chemokine receptor for their BM retention, up-regulated CCR7, and migrated to lymph nodes (LNs). We found that CDPs in the BM express TLR2, TLR4, and TLR9. Microbes are sensed by pathogen recognition receptors such as Toll-like receptors (TLRs).
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How the dissemination of progenitor-derived DCs to peripheral tissues is regulated on need remains elusive. Common dendritic cell progenitors (CDPs) in the bone marrow (BM) regenerate dendritic cells (DCs) in lymphoid and nonlymphoid tissues.