Jagannathan Madhumita, Hasturk Hatice, Liang Yanmei, Shin Hyunjin, Hetzel Jeremy T, Kantarci Alpdogan, Rubin Daniel, McDonnell Marie E, Van Dyke Thomas E, Ganley-Leal Lisa M, Nikolajczyk Barbara S
Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
J Immunol. 2009 Dec 1;183(11):7461-70. doi: 10.4049/jimmunol.0901517. Epub 2009 Nov 16.
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-1beta 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.
慢性全身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。Toll样受体（TLRs）的激活，尤其是TLR2和TLR4，会促进慢性全身炎症。人们普遍认为人类B细胞缺乏这些TLRs。然而，最近的研究表明，炎症性疾病患者循环B细胞中表达TLR2和TLR4的比例增加，并且B细胞上的TLR结合导致基因表达出现意外变化。新数据表明，炎症性疾病患者的B细胞会对不同类型的TLR配体做出反应，分泌多种细胞因子。此外，B细胞对TLR配体组合的反应具有细胞因子和配体特异性。一些细胞因子（IL-1β和IL-10）主要受TLR4调节，但其他细胞因子（IL-8和TNF-α）主要受TLR2调节，部分原因是TLR决定了转录因子/启动子关联的变化。TLR2和TLR9也调节B细胞TLR4的表达，表明TLR相互作用在多个水平上控制B细胞反应。对牙周病和糖尿病患者B细胞的平行检测表明，TLR相互作用的结果受疾病病理影响。我们得出结论，疾病相关的B细胞TLR反应改变特异性调节细胞因子产生，并可能影响慢性炎症。
