| First Author | Sha S | Year | 2021 |
| Journal | Diabetes | Volume | 70 |
| Issue | 2 | Pages | 504-515 |
| PubMed ID | 33154070 | Mgi Jnum | J:360608 |
| Mgi Id | MGI:7834557 | Doi | 10.2337/db20-0373 |
| Citation | Sha S, et al. (2021) TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model. Diabetes 70(2):504-515 |
| abstractText | Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell-specific deficiency of TLR9 (TLR9(fl/fl)/CD19-Cre+ NOD). The B-cell-specific deletion of TLR9 resulted in near-complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of interleukin-10 (IL-10)-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and CD40, all of which are interconnected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immunopathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment. |
