Booth Jayaum, Jimbo Steve, Mutwiri George
Yale School of Medicine, Yale University, New Haven, CT 06520-8019, USA.
Vet Immunol Immunopathol. 2012 Jul 15;148(1-2):157-60. doi: 10.1016/j.vetimm.2011.04.011. Epub 2011 Apr 20.
Regulation of TLR responses is required in the intestine to prevent unnecessary responses to commensal microorganisms and maintain tissue homeostasis. Several mechanisms have been proposed for the regulation of TLR responses in intestinal epithelial and lamina propria cells. However, whether this regulation occurs in Peyer's patches (PP) is not known. While investigating cellular responses to the TLR9 agonist CpG ODN, we observed that PP cells responded poorly to CpG ODN stimulation despite expressing TLR9. We hypothesized that PP cells produced the immunoregulatory cytokine IL-10 which suppressed TLR-induced cytokine responses. In vitro neutralization of IL-10 or depletion of CD21+ B cells from PP resulted in significant increases in IL-12, IFNγ and IFNα responses in PP cells stimulated with CpG ODN. Essentially, our investigation have identified a novel population of IL-10-secreting B cells in PP with regulatory functions (B(regs)). These B(regs) may play an important role in the maintenance of intestinal homeostasis.
肠道中需要对Toll样受体（TLR）反应进行调节，以防止对共生微生物产生不必要的反应并维持组织稳态。已经提出了几种机制来调节肠道上皮细胞和固有层细胞中的TLR反应。然而，这种调节是否发生在派尔集合淋巴结（PP）中尚不清楚。在研究细胞对TLR9激动剂CpG ODN的反应时，我们观察到尽管PP细胞表达TLR9，但它们对CpG ODN刺激的反应很差。我们推测PP细胞产生了免疫调节细胞因子IL-10，它抑制了TLR诱导的细胞因子反应。在体外中和IL-10或从PP中去除CD21 + B细胞，会导致用CpG ODN刺激的PP细胞中IL-12、IFNγ和IFNα反应显著增加。本质上，我们的研究已经在PP中鉴定出了一群具有调节功能的分泌IL-10的B细胞（B调节细胞）。这些B调节细胞可能在维持肠道稳态中发挥重要作用。
