Systemic lupus erythematosus （SLE） is an autoimmune disease characterized by B-cell hyperreactivity. The Toll-like receptor 7 （TLR7） signaling pathway is abnormally activated in SLE B cells. CyclinD3 （CCND3） pla...Systemic lupus erythematosus （SLE） is an autoimmune disease characterized by B-cell hyperreactivity. The Toll-like receptor 7 （TLR7） signaling pathway is abnormally activated in SLE B cells. CyclinD3 （CCND3） plays an important role in B-cell proliferation, development, and differentiation. Although previous studies focused on the B cell-intrinsic role of TLR7 for the development of spontaneous germinal centers, the influence of TLR7 on CCND3 in SLE B cells is still not clear. Here, we used a B-cell profiling chip and found that CCND3 was related to SLE and significantly elevated in SLE B cells. Moreover, we determined that the expression level of CCND3 was higher, while miR-15b was significantly lower in the B cells from SLE patients and B6.MRL-Faslpr/J lupus mice compared to normal subjects. Furthermore, we demonstrated that the activation of TLR7 dramatically increased CCND3 expression but significantly decreased miR-15b in B cells in vitro and we identified that CCND3 is a direct target of miR-15b. To further confirm our results, we established another lupus model by topically treating C57BL/6 （B6） mice with the TLR-7 agonist imiquimod （IMQ） for 8 weeks according to the previously described protocol. Expectedly, topical treatment with I MQ also significantly increased CCND3 and decreased miR-15b in B cells of B6 mice. Taken together, our results identified that the activation of TLR7 increased CCND3 expression via the downregulation of miR-15b in B cells; thus, these findings suggest that extrinsic factor-induced CCND3 expression may contribute to the abnormality of B cell in SLE.展开更多
Meyoid derived suppressor cells(MDSCs)are heterogeneous myeloid cell populations that expand in pathological conditions such as cancer,autoimmunity,and infection;these cells are also known to exert strong immunosuppre...Meyoid derived suppressor cells(MDSCs)are heterogeneous myeloid cell populations that expand in pathological conditions such as cancer,autoimmunity,and infection;these cells are also known to exert strong immunosuppressive effects on primitive Tcell responses.1 MDSCs are derived from myeloid progenitors and are arrested at an immature phase of differentiation.In mice,normal bone marrow contains~20–30%cells exhibiting the MDSC phenotype.2 In contrast,a very low number of MDSCs are found in naive spleens(2–4%),and these cells are completely absent in lymph nodes.展开更多
文摘Systemic lupus erythematosus （SLE） is an autoimmune disease characterized by B-cell hyperreactivity. The Toll-like receptor 7 （TLR7） signaling pathway is abnormally activated in SLE B cells. CyclinD3 （CCND3） plays an important role in B-cell proliferation, development, and differentiation. Although previous studies focused on the B cell-intrinsic role of TLR7 for the development of spontaneous germinal centers, the influence of TLR7 on CCND3 in SLE B cells is still not clear. Here, we used a B-cell profiling chip and found that CCND3 was related to SLE and significantly elevated in SLE B cells. Moreover, we determined that the expression level of CCND3 was higher, while miR-15b was significantly lower in the B cells from SLE patients and B6.MRL-Faslpr/J lupus mice compared to normal subjects. Furthermore, we demonstrated that the activation of TLR7 dramatically increased CCND3 expression but significantly decreased miR-15b in B cells in vitro and we identified that CCND3 is a direct target of miR-15b. To further confirm our results, we established another lupus model by topically treating C57BL/6 （B6） mice with the TLR-7 agonist imiquimod （IMQ） for 8 weeks according to the previously described protocol. Expectedly, topical treatment with I MQ also significantly increased CCND3 and decreased miR-15b in B cells of B6 mice. Taken together, our results identified that the activation of TLR7 increased CCND3 expression via the downregulation of miR-15b in B cells; thus, these findings suggest that extrinsic factor-induced CCND3 expression may contribute to the abnormality of B cell in SLE.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant number BK20180825)supported by the National Natural Science Foundation of China(31872732).
文摘Meyoid derived suppressor cells(MDSCs)are heterogeneous myeloid cell populations that expand in pathological conditions such as cancer,autoimmunity,and infection;these cells are also known to exert strong immunosuppressive effects on primitive Tcell responses.1 MDSCs are derived from myeloid progenitors and are arrested at an immature phase of differentiation.In mice,normal bone marrow contains~20–30%cells exhibiting the MDSC phenotype.2 In contrast,a very low number of MDSCs are found in naive spleens(2–4%),and these cells are completely absent in lymph nodes.
