Interferon and tumor necrosis factor as humoral mechanisms coupling hematopoietic activity to inflammation and injury

Askenasy, Nadir

doi:10.1016/j.blre.2014.09.002

Cited by 9 publications

(8 citation statements)

References 73 publications

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“…As low burden infections persisted in the intestine even after neutralization of IFN‐γ, it is possible that other factors drive blood neutrophilia such as tissue damage, other cytokines, and worm antigens induced by the physical presence of the worms. Together, these findings are consistent with the notion that the role of IFN‐γ during hematopoiesis is context dependent that will vary between different infection models. Additionally, IFN‐γ can differentially affect BM responses by synergizing with other cytokines that are likely considerably different in our model of intestinal helminth infection compared to these other experimental models.…”

Section: Discussionsupporting

confidence: 87%

Chronic Trichuris muris infection alters hematopoiesis and causes IFN‐γ‐expressing T‐cell accumulation in the mouse bone marrow

et al. 2016

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Proinflammatory cytokines produced during immune responses to infectious stimuli are well-characterized to have secondary effects on the function of hematopoietic progenitor cells in the BM. However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell-associated, but not acute Th2 cell-associated, responses to chronic T. muris infection cause a major, transient expansion of CD48 CD150 multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN-γ signaling. Chronic T. muris infection also broadly stimulated proliferation of BM progenitor cells including CD48 CD150 hematopoietic stem cells. This shift in progenitor activity during chronic T. muris infection correlated with a functional increase in myeloid colony formation in vitro as well as neutrophilia in the BM and peripheral blood. In parallel, we observed an accumulation of CD4 , CD8 , and CD4 CD8 (double negative) T cells that expressed IFN-γ, displaying activated and central memory-type phenotypes in the bone marrow during chronic infection. Thus, these results demonstrate that Th1 cell-driven responses in the intestine during chronic helminth infection potently influence upstream hematopoietic processes in the BM via IFN-γ.

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Section: Discussionsupporting

confidence: 87%

Chronic Trichuris muris infection alters hematopoiesis and causes IFN‐γ‐expressing T‐cell accumulation in the mouse bone marrow

et al. 2016

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“…Thus, IFNγR-signalling on HSCs has been viewed as a pivotal mechanism to explain alterations in HSC function under inflammatory conditions [47–50]. Likewise, a similar role was more recently suggested for HSC-intrinsic TNFR signalling during stress-induced hematopoiesis [36].…”

Section: Discussionmentioning

confidence: 95%

TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis

et al. 2017

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Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. Quiescent LT-HSCs were maintained in infected RAG2 KO mice, but lost following adoptive transfer of IFNγ-sufficient but not IFNγ-deficient CD4+ T cells. Using mixed BM chimeras, we established that IFNγ and TNF signalling pathways converge at the level of CD4+ T cells. Critically, intrinsic TNF signalling is required for the expansion and/or differentiation of pathogenic IFNγ+CD4+ T cells that promote the irreversible loss of BM function. These findings provide new insights into the pathogenic potential of CD4+ T cells that target hematopoietic function in leishmaniasis and perhaps other infectious diseases where TNF expression and BM dysfunction also occur simultaneously.

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“…Our results also showed that ghrelin decreased serum TNF-α, IL-6, and IL-1β levels in CRBI rats on days 1, 4, and 7 after injury. These indicated that ghrelin inhibits the excessive inflammatory response, enhances the recovery of hematopoietic function, and maintains the biological balance between inflammation and hematopoiesis384041.…”

Section: Discussionmentioning

confidence: 95%

Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

Liu

Huang

et al. 2016

Sci Rep

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The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways.

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Interferon and tumor necrosis factor as humoral mechanisms coupling hematopoietic activity to inflammation and injury

Cited by 9 publications

References 73 publications

Chronic Trichuris muris infection alters hematopoiesis and causes IFN‐γ‐expressing T‐cell accumulation in the mouse bone marrow

Chronic Trichuris muris infection alters hematopoiesis and causes IFN‐γ‐expressing T‐cell accumulation in the mouse bone marrow

TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis

Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

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