Adult NK lineage development in humans is strengthened upon emergency

Abstract

Emergency conditions such as infection demand rapid production and activation of innate immune cells to combat noxious extrinsic agents. In mice, pathogen recognition through Toll like receptors (TLR) and the resulting pro-inflammatory cytokine release induce the expansion of bone marrow hematopoietic stem cells and instruct early differentiation fates so immediate innate cell development is guaranteed. Accordingly, recent work suggests that human primitive cell populations are also capable of microbial components discrimination through TLR, a mechanism that facilitates their differentiation to myeloid lineage cells. We have now found that early lymphoid progenitor cells from adult bone marrow display TLR9 and its ligation promotes the quick development of NK lineage cells by using mechanisms that involve IL-15R up-regulation. Strikingly, this phenomenon is not obvious in their neonatal counterparts, suggesting that contribution of neonatal seminal cells to the emergent cell production in response to viral signals may differ from that of adult cells.

Early Differentiation of Human CD11c+NK Cells withγδT Cell Activation Properties Is Promoted by Dialyzable Leukocyte Extracts

“…Emergency hematopoiesis defines the production of functional hematopoietic cells under nonhomeostatic, proinflammatory, or biologically stressed conditions [1–4]. Blood cell production is a tightly regulated process that, after birth and throughout life, starts in a conspicuous hematopoietic stem cell (HSC) subset residing within the bone marrow (BM).…”

“…According to what mouse research has shown, human multilymphoid progenitors (MLP) are capable of responding to TLR stimulation by producing dendritic cells, and our recent work suggests that primitive early lymphoid progenitor populations are also capable of microbial components discrimination through TLR, a mechanism that mostly facilitates their differentiation to innate lymphoid lineage cells. Of special interest, TLR9 ligation on adult BM progenitors promotes the quick development of NK lineage cells by using mechanisms that involve IL-15R upregulation [4, 9]. …”