| First Author | Soni C | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 10 | Pages | 1475-1480 |
| PubMed ID | 37800687 | Mgi Jnum | J:360040 |
| Mgi Id | MGI:7568935 | Doi | 10.4049/jimmunol.2300313 |
| Citation | Soni C, et al. (2023) Cutting Edge: TLR2 Signaling in B Cells Promotes Autoreactivity to DNA via IL-6 Secretion. J Immunol 211(10):1475-1480 |
| abstractText | Autoantibodies to chromatin and dsDNA are a hallmark of systemic lupus erythematosus (SLE). In a mouse model of monogenic human SLE caused by DNASE1L3 deficiency, the anti-DNA response is dependent on endosomal nucleic acid-sensing TLRs TLR7 and TLR9. In this study, we report that this response also required TLR2, a surface receptor for microbial products that is primarily expressed on myeloid cells. Cell transfers into lymphopenic DNASE1L3-deficient mice showed that TLR2 was required for anti-DNA Ab production by lymphocytes. TLR2 was detectably expressed on B cells and facilitated the production of IL-6 by B cells activated in the presence of microbial products. Accordingly, treatment with broad-spectrum antibiotics or Ab-mediated blockade of IL-6 delayed the anti-DNA response in DNASE1L3-deficient mice. These studies reveal an unexpected B cell-intrinsic role of TLR2 in systemic autoreactivity to DNA, and they suggest that microbial products may synergize with self-DNA in the activation of autoreactive B cells in SLE. |
