https://scholars.lib.ntu.edu.tw/handle/123456789/641465
標題: | Plasmacytoid Dendritic Cells Enhance T-Independent B Cell Response through a p38 MAPK-STAT1 Axis | 作者: | Chen, Hsin-Hsiang Yu, Ya-Ru Hsiao, Yu-Ling Chen, Shun-Hua CHIEN-KUO LEE |
公開日期: | 15-八月-2023 | 出版社: | American Association of Immunologists | 卷: | 211 | 期: | 4 | 起(迄)頁: | 576-590 | 來源出版物: | Journal of Immunology | 摘要: | TLR signaling in B cells triggers their activation and differentiation independent of help from T cells. Plasmacytoid dendritic cells (pDCs) cooperate with B cells to boost TLR-stimulated T-independent humoral immunity; however, the molecular mechanisms remain elusive. In this study, we demonstrate that in the mouse system, the adjuvant effects of pDCs also occurred following challenge with pathogens and that follicular (FO) B cells were more sensitive to pDC-induced enhancement than were marginal zone (MZ) B cells. Moreover, pDCs migrated to the FO zones and interacted with FO B cells upon stimulation in vivo. CXCL10, a ligand for CXCR3 expressed on pDCs, was superinduced in the coculture system and facilitated the cooperative activation of B cells. Moreover, pDCs also promoted TLR-stimulated autoantibody production in FO B and MZ B cells. Ingenuity Pathway Analysis and gene set enrichment analysis revealed that type I IFN (IFN-I)-mediated JAK-STAT and Ras-MAPK pathways were highly enriched in R848-stimulated B cells cocultured with pDCs compared with B cells alone. Whereas IFN-I receptor 1 deficiency reduced pDC-enhanced B cell responses, STAT1 deficiency displayed a more pronounced defect. One of the STAT1-dependent but IFN-I-independent mechanisms was TLR-induced STAT1-S727 phosphorylation by p38 MAPK. Serine 727 to alanine mutation attenuated the synergism between pDCs and B cells. In conclusion, we uncover a molecular mechanism for pDC-enhanced B cell response and define a crucial role of the IFN-I/TLR-mediated signaling pathway through a p38 MAPK-STAT1 axis in controlling T-independent humoral immunity and providing a novel therapeutic target for treating autoimmune diseases. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641465 | ISSN: | 00221767 | DOI: | 10.4049/jimmunol.2200210 |
顯示於: | 免疫學研究所 |
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