Post-Doctoral Research Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China; Xinjiang Institute of Pediatrics, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830054, China.
Respiratory Department, The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi 830049, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108330. doi: 10.1016/j.intimp.2021.108330. Epub 2021 Nov 30.
The study is to investigate the roles of group 2 innate lymphoid cells (ILC2s) in different courses of tuberculosis (TB). Serum and PBMCs were respectively isolated from the TST negative, LTBI (latent TB infection), ATB (active TB) and RTB (recurrent TB) patients. Flow cytometry was used to detect Th1, Th2 and ILC2s in the peripheral blood. The mRNA and protein levels of GATA3, RORα, CRTH2, Hes1, Notch1, NF-κB, and ID2 were detected by qRT-PCR and Western blotting. ILC2 cells from ATB and RTB patients were stimulated with rJagged2 or DAPT in vitro, and co-cultured with CD4 T cells from TST negative group. ELISA was used to detect cytokine levels. The results showed that compared with the TST negative or LTBI group, Th2 cells and serum IL-4 in ATB group increased dramatically, accompanied by an increase of Th2/Th1 ratio in ATB patients, especially in RTB group. However, ILC2s in the ATB and RTB group increased significantly, along with increased GATA3, RORα, and CRTH2 levels. After rJagged2 stimulation in vitro, the levels of Hes1, Notch1, NF-κB, RORα, GATA3 and ID2 and those of IL-4, IL-5 and IL-13 were significantly increased. These effects were abrogated by DAPT treatment. Then, ILC2s, especially those from RTB patients, induced Th2-type immune response after co-culturing with CD4 T cells. In conclusion, our results suggest that ILC2s may promote Th2-type immune response in different stages of TB via the Notch-GATA3 pathway.
本研究旨在探讨 2 型固有淋巴细胞（ILC2）在不同阶段结核病（TB）中的作用。分别从结核菌素皮肤试验阴性（TST 阴性）、潜伏性结核感染（LTBI）、活动性结核（ATB）和复发性结核（RTB）患者中分离血清和 PBMCs。采用流式细胞术检测外周血中 Th1、Th2 和 ILC2。通过 qRT-PCR 和 Western blot 检测 GATA3、RORα、CRTH2、Hes1、Notch1、NF-κB 和 ID2 的 mRNA 和蛋白水平。用 rJagged2 或 DAPT 体外刺激 ATB 和 RTB 患者的 ILC2 细胞，与 TST 阴性组的 CD4 T 细胞共培养。ELISA 检测细胞因子水平。结果表明，与 TST 阴性或 LTBI 组相比，ATB 组 Th2 细胞和血清 IL-4 明显增加，ATB 患者 Th2/Th1 比值升高，尤其是 RTB 组。然而，ATB 和 RTB 组的 ILC2 明显增加，同时 GATA3、RORα 和 CRTH2 水平升高。体外经 rJagged2 刺激后，Hes1、Notch1、NF-κB、RORα、GATA3 和 ID2 的水平以及 IL-4、IL-5 和 IL-13 的水平均显著增加。DAPT 处理可阻断这些作用。然后，ILC2，特别是来自 RTB 患者的 ILC2，与 CD4 T 细胞共培养后诱导 Th2 型免疫应答。综上所述，我们的研究结果表明，ILC2 可能通过 Notch-GATA3 通路在 TB 的不同阶段促进 Th2 型免疫应答。
