TNF-α-induced programmed cell death in the pathogenesis of acquired aplastic anemia

Chen, Yongfeng; Zou, Zhenyou; Wu, Zhi‐Ying; Zhao, Zhiqiang; Luo, Xin; Xie, Conghua; Liang, Yong

doi:10.1586/17474086.2015.1049593

Cited by 25 publications

(28 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been proposed that both IFNγ and TNFα contribute to hematopoietic repression in the pathogenesis of AAA. [17][18][19]28,29 The elevated serum levels of both IFNγ and TNFα are consistent with the occurrence of BMF in our animal model (Online Supplementary Figure S15). However, we determined that these two inflammatory cytokines function in opposite ways in the pathogenesis of AAA.…”

Section: Cd4supporting

confidence: 83%

“…TNFα is thought to be a key mediator of autoimmune BMF. 28,29 However, inactivation of TNFα signaling surprisingly accelerates the progression of BMF in Tak1 mut mice, an observation which runs counter to generally accepted theory. The BMF phenotypes of Tak1 mut and Tak1 mut Tnfr -/-mice (deletion of both TNF receptor 1 and 2) resemble most of the clinical manifestations seen in chronic and severe AAA patients, respectively.…”

Section: 24mentioning

confidence: 76%

“…This observation is contrary to the currently accepted dogma for the role of TNFα in the pathogenesis of autoimmune diseases. 28,29 Based on the data we have presented in the current studies, we suggest that anti-TNF treatment should be avoided in treating patients with autoimmune-related BMF such as AAA. In fact, TNF blockade-related autoimmune BMF has been reported consistently.…”

Section: Cd4mentioning

confidence: 84%

See 2 more Smart Citations

Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

et al. 2016

View full text Add to dashboard Cite

Section: Cd4supporting

confidence: 83%

Section: 24mentioning

confidence: 76%

Section: Cd4mentioning

confidence: 84%

See 1 more Smart Citation

Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

et al. 2016

View full text Add to dashboard Cite

“…Multiple studies have demonstrated that TNF- α inhibits erythropoiesis and causes anemia in human. 34, 38, 39, 40, 41 Moreover, TNF- α can induce cell death of erythroid cells via caspase-mediated cleavage of the master regulator of erythropoiesis, GATA1. 9, 15, 42, 43, 44 Our finding that Stk40 deletion in the fetal liver causes aberrant activation of TNF- α signaling supports the idea that Stk40 plays an important role in repressing TNF- α signaling activation.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Stk40 impairs definitive erythropoiesis in the mouse fetal liver

Wang

Cheng

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

The serine threonine kinase Stk40 has been shown to involve in mouse embryonic stem cell differentiation, pulmonary maturation and adipocyte differentiation. Here we report that targeted deletion of Stk40 leads to fetal liver hypoplasia and anemia in the mouse embryo. The reduction of erythrocytes in the fetal liver is accompanied by increased apoptosis and compromised erythroid maturation. Stk40 − / − fetal liver cells have significantly reduced colony-forming units (CFUs) capable of erythroid differentiation, including burst forming unit-erythroid, CFU-erythroid (CFU-E), and CFU-granulocyte, erythrocyte, megakaryocyte and macrophage, but not CFU-granulocyte/macrophages. Purified Stk40 − / − megakaryocyte-erythrocyte progenitors produce substantially fewer CFU-E colonies compared to control cells. Moreover, Stk40 − / − fetal liver erythroblasts fail to form normal erythroblastic islands in association with wild type or Stk40 − / − macrophages, indicating an intrinsic defect of Stk40 − / − erythroblasts. Furthermore, the hematopoietic stem and progenitor cell pool is reduced in Stk40 − / − fetal livers but still retains the multi-lineage reconstitution capacity. Finally, comparison of microarray data between wild type and Stk40 − / − E14.5 fetal liver cells reveals a potential role of aberrantly activated TNF-α signaling in Stk40 depletion induced dyserythropoiesis with a concomitant increase in cleaved caspase-3 and decrease in Gata1 proteins. Altogether, the identification of Stk40 as a regulator for fetal erythroid maturation and survival provides new clues to the molecular regulation of erythropoiesis and related diseases.

show abstract

“…Although inflammatory signaling is critical during infection and inflammation, prolonged exposure to inflammatory signals including TLRs, IFNs, TNF, and IL-1 will repress the self-renewal of HSCs, which eventually results in HSC exhaustion [46,51,59,60,74,102]. Indeed, myelodysplastic syndromes (MDSs) and BMF syndromes have been associated with excessive TNF and IFNγ signaling, both of which have been proposed to contribute to the repression of hematopoietic cells [57,61,66,103].…”

Section: Necroinflammation and Bmfmentioning

confidence: 99%

Necroinflammation emerges as a key regulator of hematopoiesis in health and disease

Jost

Höckendorf

2018

Cell Death Differ

View full text Add to dashboard Cite

The hematopoietic system represents an organ system with an exceptional capacity for the production of mature blood cells from a small and mostly quiescent pool of hematopoietic stem cells (HSCs). This extraordinary capacity includes selfrenewal but also the propensity to rapidly respond to extrinsic needs, such as acute infections, severe inflammation, and wound healing. In recent years, it became clear that inflammatory signals such as cytokines, chemokine and danger signals from pathogens (PAMPs) or dying cells (DAMPs) impact on HSCs, shaping their proliferation status, lineage bias, and repopulating ability and subsequently increasing the output of mature effector cells. However, inflammatory danger signals negatively impact on the capacity of HSCs to self-renew and to maintain their stem cell capabilities. This is evidenced in conditions of chronic inflammation where bone marrow failure may originate from HSC exhaustion. Even in hematopoietic cancers, inflammatory signals shape the phenotype of the malignant clone as exemplified by necrosome-dependent inflammation elicited during malignant transformation in acute myeloid leukemia. Accordingly, understanding the contribution of inflammatory signals, and specifically necroinflammation, to HSC integrity, HSC long-term functionality, and malignant transformation has attracted substantial research and clinical interest. In this review, we highlight recent developments and open questions at the interplay between inflammation, regulated necrosis, and HSC biology in the context of blood cell development, acute and chronic inflammation, and hematopoietic cancer.

show abstract

TNF-α-induced programmed cell death in the pathogenesis of acquired aplastic anemia

Cited by 25 publications

References 81 publications

Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

Deletion of Stk40 impairs definitive erythropoiesis in the mouse fetal liver

Necroinflammation emerges as a key regulator of hematopoiesis in health and disease

Contact Info

Product

Resources

About