| First Author | Nishio N | Year | 2014 |
| Journal | Immunol Cell Biol | Volume | 92 |
| Issue | 2 | Pages | 170-80 |
| PubMed ID | 24247289 | Mgi Jnum | J:302042 |
| Mgi Id | MGI:6507469 | Doi | 10.1038/icb.2013.78 |
| Citation | Nishio N, et al. (2014) Loss of GADD34 induces early age-dependent deviation to the myeloid lineage. Immunol Cell Biol 92(2):170-80 |
| abstractText | Hematopoietic stem cells (HSCs) generate all known hematopoietic lineages and are capable of self-renewal. Upon aging, myeloid-biased HSCs are maintained, whereas lymphoid-biased HSCs are lost. GADD34 protein is expressed in myeloid-lineage cells and has been cloned from them. However, the function of GADD34 in the myeloid lineage has not yet been elucidated. Here, we show that early age-dependent deviation to the myeloid lineage occurs in GADD34-deficient mice. Early increases of GR-1(int)CD11b(+) and GR-1(high)CD11b(+) neutrophils were observed in the spleen, bone marrow (BM) and blood of GADD34-deficient mice. We found that BM Lin(-) c-Kit(+) Sca1(+) and Lin(-) c-Kit(+) Sca1(-)cells expressed GADD34 protein without stimulation and increased GADD34 expression following intravenous injection of Staphylococcus aureus (S.aureus). These cell populations were high in GADD34-deficient BM and were increased by the injection of S. aureus. Because of the increase in granulocyte colony-stimulating factor (G-CSF) induced by S. aureus injection, we examined the signaling pathway from the G-CSF receptor (G-CSFR). We found that phosphorylation of signal transducer and activator of transcription factor 3 was highly increased in GADD34-deficient Lin(-) BM cells by the stimulation of G-CSF. These results indicate that GADD34 binds to Lyn and inhibit G-CSFR signaling. We show here that GADD34 works to inhibit the proliferation and differentiation of HSCs or myeloid precursor cells and maintains homeostatic differentiation of neutrophil-lineage cells to avoid early immunological senescence. |
