Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2

Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection

“…Despite the significant variability among the different infection models, there are some conserved features: (a) Infection-derived inflammation leads frequently to HSC functional decline, including reduced repopulating capacity and increased proliferation associated with a myeloid lineage bias; (b) HSC functional decline is most commonly associated with chronic infection, which suggests that prolonged inflammation and the resultant demand may exert cumulative effects on HSC function; (c) inflammatory cytokines can act both directly on HSCs and indirectly, leading to secondary inflammatory signal production by BM niche cells, such as mesenchymal stromal cells (MSCs), endothelial cells, and mature hematopoietic cells. Overall, the studies presented in Table 1 indicate that infection-derived inflammation is a significant source of BM inflammation with the potential to establish long-term functional impairment on HSCs ( Binder et al, 1997 ; de Bruin et al, 2013 ; Matatall et al, 2014 ; Schürch et al, 2014 ; Isringhausen et al, 2020 Preprint ; Hirche et al, 2017 ; Scumpia et al, 2010 ; Burberry et al, 2014 ; Shi et al, 2018 ; Baldridge et al, 2010 ; Matatall et al, 2016 ; Florez et al, 2020 ; Choi et al, 2011 ; Khan et al, 2020 ; MacNamara et al, 2011 ; Smith et al, 2018 ; Vainieri et al, 2016 ; Haltalli et al, 2020 ; Martínez et al, 2018 ; Mitroulis et al, 2018 ).…”

Rapid Activation of Hematopoietic Stem Cells

“…Surface activation markers allow us to quantify earlier stages with a single-cell resolution (Figure 1). CD317 (BST2) has a role in anti-viral response (Le Tortorec et al, 2011), and it was also shown to play a role in the retention of HSCs within the BM (Florez et al, 2020). CD69 is a major activation marker of immune cells and a metabolic regulator (Cibrian and Sanchez-Madrid, 2017); intriguingly, CD69 is also implicated in HSC and Progenitors (HSPC) retention in the BM (Notario et al, 2018), suggesting that CD69, like CD317, may regulate their BM localization following stimulation.…”

“…We identified HSC-activation markers (Bujanover et al, 2018), including CD69 ( Clec2c ) and CD317 ( Bst2 ). These markers were validated in a brilliant study showing the essential role of CD317 for retaining activated HSCs in the proper BM niche (Florez et al, 2020). In the current work, we sought to utilize these surface markers to study how early HSC activation occurs and how sensitive HSCs are to commonly used immune stimuli.…”

Inflammation Regulates Haematopoietic Stem Cells and Their Niche

“…HSC Expansion and Differentiation: many pro-inflammatory cytokines and growth factors, for instance, granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), GM-CSF, IL-3, IL-6, TNF-α, IFNs, and Fms-related receptor tyrosine kinase 3 (Flt3) ligands, have been demonstrated to bias HSPC differentiation towards myelopoiesis at the expense of lymphopoiesis [29,30]. Some of the molecules, such as TNF-α, IL-1, and M-CSF are more potent in promoting HSC expansion [31][32][33][34][35][36][37]. Repetitive direct TLR4 activation by LPS infections has been shown to drive quiescent HSCs to cell cycling and diminish their self-renewal capacity [18,38].…”