| First Author | Soni C | Year | 2018 |
| Journal | Immunol Cell Biol | Volume | 96 |
| Issue | 3 | Pages | 298-315 |
| PubMed ID | 29345385 | Mgi Jnum | J:273106 |
| Mgi Id | MGI:6282348 | Doi | 10.1111/imcb.12003 |
| Citation | Soni C, et al. (2018) Crucial role of Mer tyrosine kinase in the maintenance of SIGN-R1(+) marginal zone macrophages. Immunol Cell Biol 96(3):298-315 |
| abstractText | Mer Tyrosine Kinase receptor (Mer) is involved in anti-inflammatory efferocytosis. Here we report elevated spontaneous germinal center (Spt-GC) responses in Mer-deficient mice (Mer(-/-) ) that are associated with the loss of SIGN-R1(+) marginal zone macrophages (MZMs). The dissipation of MZMs in Mer(-/-) mice occurs independently of reduced cellularity or delocalization of marginal zone B cells, sinusoidal cells or of CD169(+) metallophillic macrophages. We find that MZM dissipation in Mer(-/-) mice contributes to apoptotic cell (AC) accumulation in Spt-GCs and dysregulation of the GC checkpoint, allowing an expansion of DNA-reactive B cells in GCs. We further observe that bone marrow derived macrophages from Mer(-/-) mice produce more TNFalpha, and are susceptible to cell death upon exposure to ACs compared to WT macrophages. Anti-TNFalpha Ab treatment of Mer(-/-) mice is, however, unable to reverse MZM loss, but results in reduced Spt-GC responses, indicating that TNFalpha promotes Spt-GC responses in Mer(-/-) mice. Contrary to an anti-TNFalpha Ab treatment, treatment of Mer(-/-) mice with a synthetic agonist for the transcription factor LXRalpha rescues a significant number of MZMs in vivo. Our data suggest that Mer-LXRalpha signaling plays an important role in the differentiation and maintenance of MZMs, which in turn regulate Spt-GC responses and tolerance. |
