IFNgamma Induces Expansion of Hematopoietic Progenitor Cells

Abstract The balance between type 1 and type 2 helper T (Th1 and Th2) cells is critical for homeostasis of the immune system, since their distinct cytokine production profile directly determines the activation and functions of other immune cells. However, as the end-differentiated lineage cells, how these effector T cells influence the hematopoietic progenitor cells, is largely unknown. Here we showed that Th1 cell products, but not those of Th2 cells, caused a remarkable expansion o f lineage-Sca-1+C-kit+ (LSK) cells. IFNgamma was found to play a major role in this expansion by activating the expression of Sca-1 in lineage-Sca-1-C-kit+ cells, thus converting them into LSK cells. This process was dependent on IFNgammaR1 signaling, but only partially mediated by STAT1 pathway. Furthermore, such IFNgamma-induced LSK cells had a significantly higher colony forming units (CFUs), compared to control lineage-Sca-1-C-kit+ cells and control LSK cells, which might compensate for the loss of progenitor cells caused by the IFNgamma-treatment. Moreover, the IFNgamma-induced expanded LSK cells were verified as functional stem/progenitor cells through the competitive repopulation experiments in vivo. Finally, the IFNgamma-induced hematopoiesis was more biased toward the differentiation of myeloid lineages in vitro and in vivo. Therefore, our findings demonstrated a novel role of IFNgamma in hematopoiesis, thus providing a new insight into the clinical application of IFNgamma.