HAEMATOLOGICA: TGFβ signaling alters acute immune response memory and leads to bone marrow failure

In view of the low and abnormal conditions of the three lines of cells, it is more common in bone marrow failure disease (BMF).
It can be divided into two types: congenital and acquired.
Acquired BMF is divided into primary and secondary.
Among them, the common The disease is aplastic anemia (AA)
.

Bone marrow failure syndrome (BMF) is characterized by impaired fitness of hematopoietic stem cells (HSC) leading to failure of hematopoietic function

It is more common in bone marrow failure disease (BMF), which can be divided into congenital and acquired.

Despite the discovery of genetic driver mutations, the hematopoietic manifestations of the disease are quite heterogeneous, which increases the possibility of non-genetic factors participating in the pathogenesis of the disease

Therefore, in a study, a research team tested the effect of polyinosine polycytic acid (pIC) on the hematopoietic system in combination with an acute innate immune attack with an increase in the TGFβ signaling pathway in the absence of genetic mutations
.

Therefore, in a study, a research team tested the effect of the use of polyinosine polycytic acid (pIC) on the hematopoietic system of an increase in the TGFβ signaling pathway in the absence of genetic mutations in combination with acute innate immune attacks
.

Detected the increase of TGFβ signaling pathway in the absence of genetic mutations in combination with acute innate immune attack and the effect of polyinosine polycytic acid (pIC) on the hematopoietic system Detected the increase of TGFβ signaling pathway in the absence of genetic mutations acute innate immune attack using inosine joint multi polytope acid (pIC) effects on the hematopoietic system, immune

Cross the transgenic Tg-b1glo+/Flox mice with Mx1-Cre mice to generate MxCre+; Tg-b1glo+/Flox(TgCre+) and MxCre−; Tg-b1glo+/Flox mice (TgCre-)
.

Three injections of 10 mg/kg/mouse polyinosine:polycytidylic acid (pIC, GEHealthcarce) every other day induced Cre recombinase expression

Cross the transgenic Tg-b1glo+/Flox mice with Mx1-Cre mice to generate MxCre+; Tg-b1glo+/Flox(TgCre+) and MxCre−; Tg-b1glo+/Flox mice (TgCre-)

Figure 1: Active TGFβ1 overexpressing mice will not show an obvious hematopoietic phenotype during steady-state hematopoiesis

Figure 2: Mice overexpressing active TGFβ1 developed ineffective hematopoietic function and cell dysplasia after acute pIC stress
.

Figure 2: Mice overexpressing active TGFβ1 developed ineffective hematopoietic function and cell dysplasia after acute pIC stress
.

Figure 2: Mice overexpressing active TGFβ1 developed ineffective hematopoietic function and cell dysplasia after acute pIC stress

Figure 3: Activated tgf β1 overexpression SLAM hematopoietic stem cells show unique transcription characteristics for a long time after acute pIC stress
.

Figure 3: Activated tgf β1 overexpression SLAM hematopoietic stem cells show unique transcription characteristics for a long time after acute pIC stress
.

Figure 3: Activated tgf β1 overexpression SLAM hematopoietic stem cells show unique transcription characteristics for a long time after acute pIC stress

Figure 4: SLAM hematopoietic stem cells overexpressed by tgf β1 show sustained mitochondrial activity and caspase-1 activity for a long time after acute pIC stress
.

Figure 4: SLAM hematopoietic stem cells overexpressed by tgf β1 show sustained mitochondrial activity and caspase-1 activity for a long time after acute pIC stress
.

Figure 4: SLAM hematopoietic stem cells overexpressed by tgf β1 show sustained mitochondrial activity and caspase-1 activity for a long time after acute pIC stress

The study found that the acute round of pIC alone drives benign age-related bone marrow cell expansion, and the increase in TGFβ signaling alone leads to mild anemia in elderly mice
.

In sharp contrast, 3-4 months after stress, the TGFβ signaling pathway increased, coupled with acute pIC stimulation, resulted in chronic pancytopenia, enlarged hematopoietic stem and progenitor cell pools, increased bone marrow dysplasia, and similar phenotypes In human bone marrow failure syndrome
.
In mechanism, this disease phenotype is uniquely related to the increase of mitochondrial content, the increase of reactive oxygen species and the enhancement of caspase-1 activity
.

The study found that the acute round of pIC alone drives benign age-related bone marrow cell expansion, and the increase in TGFβ signaling alone leads to mild anemia in elderly mice
.
The acute round of pIC alone drives the benign age-related expansion of bone marrow cells, and the increase in TGFβ signaling alone leads to mild anemia in elderly mice
.
In sharp contrast, 3-4 months after stress, the TGFβ signaling pathway increased, coupled with acute pIC stimulation, resulted in chronic pancytopenia, enlarged hematopoietic stem and progenitor cell pools, increased bone marrow dysplasia, and similar phenotypes In human bone marrow failure syndrome
.
In mechanism, this disease phenotype is uniquely related to the increase of mitochondrial content, the increase of reactive oxygen species and the enhancement of caspase-1 activity
.
In the 3-4 months after stress, the TGFβ signaling pathway increases, coupled with acute pIC stimulation, leads to chronic pancytopenia, enlarges the pool of hematopoietic stem and progenitor cells, increases bone marrow dysplasia, and the phenotype is similar to human bone marrow failure syndrome
.
In mechanism, this disease phenotype is uniquely related to the increase of mitochondrial content, the increase of reactive oxygen species and the enhancement of caspase-1 activity
.

In summary, the results of the study showed that chronic increased TGFβ signal change memory acute immune response, leading to bone marrow failure , genetic damage without the need for pre-existing
.
Therefore, the combination of non-genetic factors is sufficient to cause bone marrow failure
.

In summary, the results of the study showed that chronic increased TGFβ signal change memory acute immune response, leading to bone marrow failure , genetic damage without the need for pre-existing
.
Therefore, the combination of non-genetic factors is sufficient to cause bone marrow failure
.
In summary, the results of the study showed that chronic increased TGFβ signal change memory acute immune response, leading to bone marrow failure , genetic damage without the need for pre-existing
.
The chronically increased TGFβ signal changes the memory of the acute immune response, and the chronically increased TGFβ signal causes the bone marrow failure to change the memory of the acute immune response, leading to bone marrow failure without the need for pre-existing genetic damage
.
Without pre-existing genetic damage
.
Therefore, the combination of non-genetic factors is sufficient to cause bone marrow failure
.
Therefore, the combination of non-genetic factors is sufficient to cause bone marrow failure
.
Therefore, the combination of non-genetic factors is sufficient to cause bone marrow failure
.

 

Original source:

Original source:

Javier J,Hinge A,Bartram J,et al.
TGFβ signaling modifies hematopoietic acute inflammatory response to drive bone marrow failure.
[J].
Haematologica,1970,:.

Javier J,Hinge A,Bartram J,et al.
TGFβ signaling modifies hematopoietic acute inflammatory response to drive bone marrow failure.
[J].
Haematologica,1970,:.
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