| First Author | Liu L | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 1308 |
| PubMed ID | 29358664 | Mgi Jnum | J:260162 |
| Mgi Id | MGI:6148377 | Doi | 10.1038/s41598-018-19827-8 |
| Citation | Liu L, et al. (2018) Delayed onset of autoreactive antibody production and M2-skewed macrophages contribute to improved survival of TACI deficient MRL-Fas/Lpr mouse. Sci Rep 8(1):1308 |
| abstractText | Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is indicated for the treatment of patients with active systemic lupus erythematosus (SLE). We hypothesized that the BAFF receptor, transmembrane activator and calcium-modulator and cyclophilin interactor (TACI) may be responsible for the generation of antibody secreting plasma cells in SLE. To test this hypothesis, we generated TACI deficient MRL-Fas/Lpr (LPR-TACI-/-) mouse. TACI deficiency resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti-dsDNA and anti-SAM/RNP antibodies. There was also a delay in the onset of proteinuria and the accumulation of IgG and inflammatory macrophages (Mvarphis) in the glomeruli of young LPR-TACI-/- mice compared to wild-type mice. Underscoring the role of TACI in influencing Mvarphi phenotype, the transfer of Mvarphis from 12-week-old LPR-TACI-/- mice to age-matched sick wild-type animals led to a decrease in proteinuria and improvement in kidney pathology. The fact that, in LPR-TACI-/- mouse a more pronounced delay was in IgM and IgG3 autoreactive antibody isotypes and the kinetics of follicular helper T (Tfh) cell-development was comparable between the littermates suggest a role for TACI in T cell-independent autoantibody production in MRL-Fas/Lpr mouse prior to the onset of T cell-dependent antibody production. |
