TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients
TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients
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DOI：
10.4049/jimmunol.0901517
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发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Nikolajczyk, Barbara S.
中科院分区：
文献类型：
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作者：
Jagannathan, Madhumita;Hasturk, Hatice;Nikolajczyk, Barbara S.
慢性全身性炎症将牙周病和糖尿病与严重合并症的发病率增加联系起来。TLR，特别是TLR 2和TLR 4的活化促进慢性全身性炎症。人类B细胞通常被认为缺乏这些TLR。然而，最近的研究表明，来自炎性疾病患者的循环B细胞表达TLR 2和TLR 4的百分比增加，并且B细胞上的TLR接合导致基因表达的意外变化。新的数据显示，来自炎性疾病患者的B细胞分泌多种细胞因子以响应不同类别的TLR配体。此外，对TLR配体组合的B细胞应答是细胞因子和配体特异性的。一些细胞因子（IL-1 β和IL-10）主要受TLR 4调节，但其他细胞因子（IL-8和TNF-α）主要受TLR 2调节，部分原因是转录因子/启动子关联中TLR决定的变化。TLR 2和TLR 9还调节B细胞TLR 4表达，表明TLR串扰在多个水平上控制B细胞应答。牙周病和糖尿病患者的B细胞的平行检查表明TLR串扰的结果受疾病病理学的影响。我们的结论是疾病相关的改变B细胞TLR反应特异性调节细胞因子的产生，并可能影响慢性炎症。免疫学杂志，2009，183：7461-7470。
Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1 beta and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-alpha) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation. The Journal of Immunology, 2009, 183: 7461-7470.