Abstract
Paired immunoglobulin-like receptor B (Pir-B) was an inhibitory receptor expressed on the surfaces of dendritic cells (DCs). Pir-B inhibit T helper (Th) 1 response and induce Th2 cell differentiation, leading to the imbalance of Th1/Th2 cells. However, the role and potential mechanism of Pir-B on the balance of Th17/regulatory T cells (Tregs) is still largely unknown in lung cancer murine model. In the present study, the DC function and Th17/Treg balance were destroyed during the progression of lung cancer and this was accompanied by an increased expression of Pir-B. After transfection with Pir-B siRNA or administration of IL-6 in vitro, the decreased response of Th17 cells were restored, whereas the augmented differentiation of Tregs was diminished. Further, the transfer of Pir-B silenced DCs or the injection of IL-6 in vivo increased Th17 response and decreased Treg differentiation. Our study has demonstrated that Pir-B inhibits the DC function and disturbs the Th17/Treg balance via IL-6 pathway during the progression of lung cancer, contributing to inhibited antitumor immunity.
Highlights
Lung cancer is the leading cause of cancer-related death in China with a tendency to metastasize widely during the course of the disease [1]
Our study has demonstrated that Paired immunoglobulin-like receptor B (Pir-B) inhibits the dendritic cells (DCs) function and disturbs the Th17/regulatory T cells (Tregs) balance via IL-6 pathway during the progression of lung cancer, contributing to inhibited antitumor immunity
The percentage of Th17 cells (CD4+ IL-17+) in tumor-bearing mice was significantly lower, whereas the percentage of Tregs (CD25+ Foxp3+) in tumorbearing mice was higher at 3, 5 and 7 weeks after Lewis lung cancer (LLC) inoculation than that in Control (Figure 2A–2D). These data confirmed that the Th17/Treg balance was disturbed during the progression of lung cancer, and this imbalance lead to tumor related immunosupression
Summary
Lung cancer is the leading cause of cancer-related death in China with a tendency to metastasize widely during the course of the disease [1]. Studies suggest that the adaptive immune system is identified as an indispensable participant of tumor immune pathogenesis [3, 4]. As the important components of adaptive immune system, CD4+ T cell subsets initiate different immune responses, and the balance between antitumor immunity and tumor immune evasion determines the direction of the malignant process [5,6,7]. Previous studies indicated that Th1 cells augmented antitumor responses, whereas Th2 cells downregulated antitumor immunity, and the balance of Th1/Th2 was disturbed during the progression of lung cancer, contributing to tumor related immunosuppression [8]. IL-17 deficiency or IL-17 blockade led to suppression of lung metastasis in tumor model, indicating that IL-17mediated responses promotes tumor development [12]. Tumor growth in subcutaneous tissue and lung tumor metastasis are enhanced in IL-17−/− mice [13, 14]
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