B10 cells decrease fibrosis progression following cardiac injury partially by IL-10 production and regulating hyaluronan secretion
B10 cells decrease fibrosis progression following cardiac injury partially by IL-10 production and regulating hyaluronan secretion
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B10 细胞部分通过产生 IL-10 和调节乙酰透明质酸分泌来减少心脏损伤后的纤维化进展。
DOI：
10.1002/jlb.3a0121-003rr
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发表时间：
2021-05-19
影响因子：
5.5
通讯作者：
Su, Zhaoliang
中科院分区：
文献类型：
--
作者：
Chen, Rong;Liu, Fang;Su, Zhaoliang
B10细胞通过产生IL-10在炎症性疾病中发挥负面作用。然而，它们对纤维化的影响还没有被阐明。因此，本研究旨在探讨B10细胞频率的动态变化及其在心肌纤维化中的潜在作用。我们发现B10细胞的频率显著增加，它们通过IL-10参与纤维化的消退，特别是通过促进透明质酸分泌和抑制胶原沉积。在体内，透明质酸消融或治疗显著限制了心肌纤维化的发展。透明质酸诱导的M1/M2 Mc的转换依赖于透明质酸的大小。低相对分子质量透明质酸促进M_1M_(Phi)的转化，而中、高相对分子质量透明质酸则促进M_(Phi)向M_2转分化。过继转移B10细胞显著减少了胶原沉积，而B10细胞减少的CD19(-/-)小鼠则加剧了心脏损伤后的纤维化。我们的结果提供了新的证据，表明B10细胞在心脏损伤过程中通过调节细胞外基质成分发挥抗纤维化作用，并强调B10细胞可能成为治疗心脏纤维化相关疾病的有前途的候选细胞。
B10 cells play negative roles in inflammatory disorders by producing IL-10. However, their effects on fibrosis have not been elucidated. Therefore, this study was conducted to examine the dynamic changes of B10 cell frequency and their potential role in cardiac fibrosis. We found that the frequency of B10 cells was significantly increased, and they participated in the regression of fibrosis via IL-10, particularly by accelerating hyaluronan secretion and inhibiting collagen deposition. In vivo, hyaluronan ablation or treatment significantly restricted cardiac fibrosis development. hyaluronan-induced conversion of M1/M2 Mc was dependent on the size of hyaluronan. Low molecular weight hyaluronan promoted the conversion to M1 M phi, whereas medium and high molecular weight hyaluronan accelerated M phi transdifferentiation into the M2 phenotype. Adoptive transfer of B10 cells significantly attenuated collagen deposition whereas CD19(-/-) mice with reduced B10 cells exacerbated fibrosis following cardiac injury. Our results provide new evidence suggesting that B10 cells exert antifibrotic effects by regulating the extracellular matrix composition during cardiac injury, and also highlight that B10 cells may serve as a promising therapeutic candidate for managing cardiac fibrosis-associated disorders.