| First Author | Xue J | Year | 2023 |
| Journal | Lupus Sci Med | Volume | 10 |
| Issue | 2 | PubMed ID | 37500293 |
| Mgi Jnum | J:358470 | Mgi Id | MGI:7780297 |
| Doi | 10.1136/lupus-2023-000974 | Citation | Xue J, et al. (2023) Impaired regulatory function of granzyme B-producing B cells against T cell inflammatory responses in lupus mice. Lupus Sci Med 10(2) |
| abstractText | OBJECTIVE: Recently, a new subtype of granzyme B (GrB)-producing Breg cells has been identified, which was proven to be involved in autoimmune disease. Our recent report demonstrated that GrB-producing Breg cells were correlated with clinical and immunological features of SLE. However, the effect of GrB-producing Breg cells in lupus mice is unclear. METHODS: GrB expression in naive and lupus mouse B cells was analysed using flow cytometry, PCR, ELISA and ELISpot assays. To study the role of GrB-producing B cells in a lupus model, GrB knockout (KO) and wild-type (WT) mice were intraperitoneally injected with monoclonal cells from the mutant mouse strain B6.C-H-2bm12 (bm12) for 2 weeks. In addition, the function of GrB-producing Breg cells in naive and lupus mice was further explored using in vitro B cells-CD4(+)CD25(-) T cell co-culture assays with GrB blockade/KO of B cells. RESULTS: B cells from the spleens of WT C57BL/6 (B6) mice could express and secret GrB (p<0.001). GrB-producing Breg cells from WT mice showed their regulatory functions on CD4(+)CD25(-) T cell. While the frequency of GrB-producing Breg cells was significantly decreased (p=0.001) in lupus mice (p<0.001). Moreover, GrB-producing Breg cells in lupus mice failed to suppress T cell-mediated proinflammatory responses, partially due to the impaired capacity of downregulating the T cell receptor-zeta chain and inducing CD4(+)CD25(-) T cell apoptosis. CONCLUSION: This study further revealed the function and mechanism of GrB-producing Breg cells in regulating T cell homeostasis in lupus mice and highlighted GrB-producing Breg cells as a therapeutic target in SLE. |
