Yin and Yang: The dual effects of interferons on hematopoiesis

Abstract

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Transcriptional reprogramming in neonatal hematopoietic stem and progenitor cells

“…The role of type I IFN during late gestation contrasts with its role in hematopoiesis at other stages of ontogeny [99]. During midgestation, type I IFN promotes HSC emergence from the dorsal aorta [100,101].…”

“…In adulthood, type I IFN signaling promotes HSC proliferation and emergency megakaryopoiesis [102−104]. IFN signaling has also drawn expanding scrutiny for its role in clonal hematopoiesis, HSC exhaustion, and malignant transformation [10,99]. Thus, the late gestation/perinatal switch adds to a growing list of roles for type I IFN signaling in normal and abnormal hematopoiesis.…”

Transforming growth factor-β signaling modifies the hematopoietic acute inflammatory response to drive bone marrow failure

“…Several studies have previously demonstrated the role of innate immune signaling in the development of BMF and MDS 5,6 . The effects of multiple inflammatory stressors are however poorly defined.…”

“…Yet, BMFS are quite heterogenous disorders raising the interest in understanding which additional factors contribute to the disease development, in addition to driver mutations. Substantial clinical data show that hyperactivity of inflammatory cytokines, including TNFα, IL-6, and transforming growth factor-β (TGFβ), as well as innate immune signaling pathways contribute to the pathogenesis of bone marrow failures 5,6 . In particular, the TGFβ signaling pathway is known to be hyperactive in Fanconi anemia 7 , myelodysplastic syndromes, [8][9][10][11] , Shwachman-Diamond syndrome 12 , myelofibrosis 13 .…”

Direct and indirect anti-leukemic properties of activity-on-target interferons for the treatment of T-cell acute lymphoblastic leukemia

“…4 The pleiotropic anti-cancer effects induced by IFN-I result from a combination of i) direct cancer cell growth inhibition by inducing cell cycle arrest, apoptosis, differentiation, and ii) indirect effects by the activation of the immune system involving antigen presentation by dendritic cells (DCs) and priming of cytotoxic CD8 + T-cells (CTLs). 5 As such, this cytokine, with both a direct and indirect immunostimulatory anti-cancer effect, is unique in its kind. Nevertheless, IFN-I therapy experienced variable and unpredictable success in the clinic.…”