| First Author | Qian B | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114249 |
| PubMed ID | 38758648 | Mgi Jnum | J:350664 |
| Mgi Id | MGI:7658721 | Doi | 10.1016/j.celrep.2024.114249 |
| Citation | Qian B, et al. (2024) Podocyte SIRPalpha reduction aggravates lupus nephritis via promoting T cell inflammatory responses. Cell Rep 43(5):114249 |
| abstractText | Signal-regulatory protein alpha (SIRPalpha) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPalpha controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPalpha under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPalpha exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPalpha deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPalpha knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPalpha loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN. |
