| First Author | Rückerl D | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 11 | Pages | 2307-16 |
| PubMed ID | 22855601 | Mgi Jnum | J:191312 |
| Mgi Id | MGI:5461435 | Doi | 10.1182/blood-2012-02-408252 |
| Citation | Ruckerl D, et al. (2012) Induction of IL-4Ralpha-dependent microRNAs identifies PI3K/Akt signaling as essential for IL-4-driven murine macrophage proliferation in vivo. Blood 120(11):2307-16 |
| abstractText | Macrophage (MPhi) activation must be tightly controlled to preclude overzealous responses that cause self-damage. MicroRNAs promote classical MPhi activation by blocking antiinflammatory signals and transcription factors but also can prevent excessive TLR signaling. In contrast, the microRNA profile associated with alternatively activated MPhi and their role in regulating wound healing or antihelminthic responses has not been described. By using an in vivo model of alternative activation in which adult Brugia malayi nematodes are implanted surgically in the peritoneal cavity of mice, we identified differential expression of miR-125b-5p, miR-146a-5p, miR-199b-5p, and miR-378-3p in helminth-induced MPhi. In vitro experiments demonstrated that miR-378-3p was specifically induced by IL-4 and revealed the IL-4-receptor/PI3K/Akt-signaling pathway as a target. Chemical inhibition of this pathway showed that intact Akt signaling is an important enhancement factor for alternative activation in vitro and in vivo and is essential for IL-4-driven MPhi proliferation in vivo. Thus, identification of miR-378-3p as an IL-4Ralpha-induced microRNA led to the discovery that Akt regulates the newly discovered mechanism of IL-4-driven macrophage proliferation. Together, the data suggest that negative regulation of Akt signaling via microRNAs might play a central role in limiting MPhi expansion and alternative activation during type 2 inflammatory settings. |
