BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth.
BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth.
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B细胞激活因子（BAFF）和增殖诱导配体（APRIL）对炎症诱导的早产易感性起反向调节作用。
DOI：
10.1016/j.celrep.2023.112352
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发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
临床证据表明，B细胞激活因子(BAFF)在妊娠中具有一定的作用。然而，BAFF轴成员在怀孕中的直接作用还没有被研究过。在这里，通过利用转基因小鼠，我们报告了BAFF促进炎症反应并增加炎症诱导的早产(PTB)的易感性。相反，我们发现密切相关的A增殖诱导配体(APRIL)降低了炎性反应和对肺结核的易感性。已知的BAFF轴受体在孕期传递BAFF/APRIL存在的信号方面起着多余的作用。用抗BAFF/APRIL单抗或BAFF/APRIL重组蛋白治疗足以控制对肺结核的易感性。值得注意的是，母胎界面的巨噬细胞产生BAFF，而BAFF和APRIL的存在不同地影响巨噬细胞的基因表达和炎症功能。总体而言，我们的发现表明，BAFF和APRIL在妊娠期间扮演着不同的炎症角色，并为降低炎症诱导的肺结核的风险提供了治疗靶点。多尔等人的研究成果。证明B细胞激活因子(BAFF)促进炎症反应和早产的易感性，而密切相关的增殖诱导配体(APRIL)则介导相反的作用。值得注意的是，BAFF和APRIL在怀孕中扮演着不同的角色，可以作为治疗的靶点，以降低炎症诱导的早产的风险。
Clinical evidence points to a function for B cell-activating factor (BAFF) in pregnancy. However, direct roles for BAFF-axis members in pregnancy have not been examined. Here, via utility of genetically modified mice, we report that BAFF promotes inflammatory responsiveness and increases susceptibility to inflammation-induced preterm birth (PTB). In contrast, we show that the closely related A proliferation-inducing ligand (APRIL) decreases inflammatory responsiveness and susceptibility to PTB. Known BAFF-axis receptors serve a redundant function in signaling BAFF/APRIL presence in pregnancy. Treatment with anti-BAFF/APRIL monoclonal antibodies or BAFF/APRIL recombinant proteins is sufficient to manipulate susceptibility to PTB. Notably, macrophages at the maternal-fetal interface produce BAFF, while BAFF and APRIL presence divergently shape macrophage gene expression and inflammatory function. Overall, our findings demonstrate that BAFF and APRIL play divergent inflammatory roles in pregnancy and provide therapeutic targets for mitigating risk of inflammation-induced PTB. Doll et al. demonstrate that B cell-activating factor (BAFF) promotes inflammatory responsiveness and susceptibility to preterm birth while the closely related a proliferation-inducing ligand (APRIL) mediates the opposite effect. Notably, BAFF and APRIL play divergent roles in pregnancy and could be therapeutically targeted for mitigating risk of inflammation-induced preterm birth.
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DOI：
10.1146/annurev-pathmechdis-012418-012743
发表时间：
2019-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Deshmukh H;Way SS
通讯作者：
Way SS
影响因子：
15.9
作者：
Hirota, Yasushi;Daikoku, Takiko;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.
影响因子：
3.4
作者：
Crespo ÂC;van der Zwan A;Ramalho-Santos J;Strominger JL;Tilburgs T
通讯作者：
Tilburgs T
影响因子：
82.9
作者：
Huang B;Faucette AN;Pawlitz MD;Pei B;Goyert JW;Zhou JZ;El-Hage NG;Deng J;Lin J;Yao F;Dewar RS 3rd;Jassal JS;Sandberg ML;Dai J;Cols M;Shen C;Polin LA;Nichols RA;Jones TB;Bluth MH;Puder KS;Gonik B;Nayak NR;Puscheck E;Wei WZ;Cerutti A;Colonna M;Chen K
通讯作者：
Chen K
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG