| First Author | McPeak MB | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 102 |
| Issue | 2 | Pages | 191-200 |
| PubMed ID | 28476751 | Mgi Jnum | J:247885 |
| Mgi Id | MGI:5926359 | Doi | 10.1189/jlb.4HI1216-537R |
| Citation | McPeak MB, et al. (2017) Frontline Science: Myeloid cell-specific deletion of Cebpb decreases sepsis-induced immunosuppression in mice. J Leukoc Biol 102(2):191-200 |
| abstractText | Sepsis inflammation accelerates myeloid cell generation to compensate for rapid mobilization of the myeloid progenitors from bone marrow. This inflammation-driven myelopoiesis, however, generates myeloid progenitors with immunosuppressive functions that are unable to differentiate into mature, innate immune cells. The myeloid-derived suppressor cells (MDSCs) expand markedly in the later phases of sepsis, suppress both innate and adaptive immunity, and thus, elevate mortality. Using a murine model with myeloid-restricted deletion of the C/EBPbeta transcription factor, we show that sepsis-induced generation of MDSCs depends on C/EBPbeta. C/EBPbeta myeloid cell-deficient mice did not generate MDSCs or develop immunosuppression and survived sepsis. However, septic mice still generated Gr1+CD11b+ myeloid progenitors at the steady-state levels similar to the control sham mice, suggesting that C/EBPbeta is not involved in healthy, steady-state myelopoiesis. C/EBPbeta-deficient Gr1+CD11b+ cells generated fewer monocyte- and granulocyte-like colonies than control mice did, indicating reduced proliferation potential, but differentiated normally in response to growth factors. Adoptive transfer of C/EBPbeta-deficient Gr1+CD11b+ cells from late septic mice exacerbated inflammation in control mice undergoing early sepsis, confirming they were not immunosuppressive. These results show that C/EBPbeta directs a switch from proinflammatory to repressor myeloid cells and identifies a novel treatment target. |
