Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis
10.16250/j.32.1374.2024013
- VernacularTitle:LAG3缺陷对多房棘球蚴感染小鼠自然杀伤细胞功能 及肝纤维化的影响
- Author:
Rousu ZIBIGU
1
,
2
,
3
;
Ainiwaer ABIDAN
1
,
2
;
Duolikun ADILAI
1
,
2
;
Yinshi LI
1
,
2
;
Xuejiao KANG
1
,
2
;
Qian YU
1
,
2
;
Bingqing DENG
1
,
2
;
Xuran ZHENG
1
,
2
;
Maolin WANG
4
;
Jing LI
1
,
3
;
Hui WANG
1
,
2
;
Chuanshan ZHANG
1
,
2
Author Information
1. College of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang 830017, China
2. Clinical Medicine Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China
3. Xinjiang Uygur Autonomous Region Key Laboratory of Molecular Biology for Endemic Diseases, Urumqi, Xinjiang 830054, China
4. Center for Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China
- Publication Type:Journal Article
- Keywords:
Echinococcus multilocularis;
Lymphocyte activation gene 3;
Natural killer cell;
Hepatic fibrosis;
Mouse
- From:
Chinese Journal of Schistosomiasis Control
2024;36(1):59-66
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.
