RESUMEN
Advances in human stem cell technologies enable induced pluripotent stem cells (iPSCs) to be explored as potent candidates for treating various diseases, such as malignancies, autoimmunity, immunodeficiencies, and allergic reactions. iPSCs with infinite self-renewal ability can be derived from different types of somatic cells without the ethical issues associated with embryonic stem cells. To date, numerous cell types, including various immune cell subsets [CD4+ and CD8+ T cells, gamma delta T (γδ T) cells, regulatory T cells, dendritic cells, natural killer cells, macrophages, and neutrophils] have successfully been generated from iPSCs paving the way for effective adoptive cell transfer therapy, drug development, and disease modeling. Herein, we review various iPSC-derived immune cells and their possible application in immunotherapy.
RESUMEN
IFN-γ, a type 2 interferon and a cytokine, is critical for both innate and adaptive immunity. IFN-γ binds to the IFN-γRs on the cell membrane of macrophages, signals through JAK1-STAT-1 pathway and induces IFN-γ-stimulated genes (ISGs). As Leishmania amastigotes reside and replicate within macrophages, IFN-γ mediated macrophage activation eventuate in Leishmania elimination. As befits the principle of parasitism, the impaired IFN-γ responsiveness in macrophages ensures Leishmania survival. IFN-γ responsiveness is a function of integrated molecular events at multiple levels in the cells that express IFN-γ receptors. In Leishmania-infected macrophages, reduced IFN-γRα expression, impaired IFN-γRα and IFN-γRß hetero-dimerization due to altered membrane lipid composition, reduced JAK-1 and STAT-1 phosphorylation but increased STAT-1 degradation and impaired ISGs induction collectively determine the IFN-γ responsiveness and the efficacy of IFN-γ induced antileishmanial function of macrophages. Therefore, parasite load is not only decided by the levels of IFN-γ produced but also by the IFN-γ responsiveness. Indeed, in Leishmania-infected patients, IFN-γ is produced but IFN-γ signalling is downregulated. However, the molecular mechanisms of IFN-γ responsiveness remain unclear. Therefore, we review the current understanding of IFN-γ responsiveness of Leishmania-infected macrophages.