| First Author | Lu Y | Year | 2020 |
| Journal | Immunity | Volume | 52 |
| Issue | 5 | Pages | 782-793.e5 |
| PubMed ID | 32272082 | Mgi Jnum | J:288601 |
| Mgi Id | MGI:6432030 | Doi | 10.1016/j.immuni.2020.03.006 |
| Citation | Lu Y, et al. (2020) Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages. Immunity 52(5):782-793.e5 |
| abstractText | Splenic red pulp macrophages (RPMs) contribute to erythrocyte homeostasis and are required for iron recycling. Heme induces the expression of SPIC transcription factor in monocyte-derived macrophages and promotes their differentiation into RPM precursors, pre-RPMs. However, the requirements for differentiation into mature RPMs remain unknown. Here, we have demonstrated that interleukin (IL)-33 associated with erythrocytes and co-cooperated with heme to promote the generation of mature RPMs through activation of the MyD88 adaptor protein and ERK1/2 kinases downstream of the IL-33 receptor, IL1RL1. IL-33- and IL1RL1-deficient mice showed defective iron recycling and increased splenic iron deposition. Gene expression and chromatin accessibility studies revealed a role for GATA transcription factors downstream of IL-33 signaling during the development of pre-RPMs that retained full potential to differentiate into RPMs. Thus, IL-33 instructs the development of RPMs as a response to physiological erythrocyte damage with important implications to iron recycling and iron homeostasis. |
