Interleukin 33 ameliorates disturbance of regulatory T cells in pulmonary sarcoidosis
INTERNATIONAL IMMUNOPHARMACOLOGY
Authors: Zhang, Bin; Zhao, Fan; Mao, Huimin; Ma, Wenyan; Zhang, Yang; Zhang, Xinyu; Ding, Jingjing; Gao, Qian; Wen, Yanting
Abstract
The feature of pulmonary sarcoidosis is characterized by a Th1/Th17/regulatory T cells (Tregs) -driven inflammatory process in lung, resulting in noncaseating granulomas containing CD4 + T cells. Tregs increase in both lung and peripheral blood, with damaged immunoregulatory function. The current study investigated the effects of IL33 or anti-IL23 antibody on restoring the homeostasis and functions of Tregs in mycobacterial superoxide dismutase A (SodA)-induced pulmonary sarcoidosis. IL33 or anti-IL23 antibody was administered to mice with late-stage pulmonary sarcoidosis. The levels of Th1/Th17/Tregs and Tregs' suppressive functions were detected by fluorescence activated cell sorting (FACS) analysis or qPCR. The expressions of key proteins in PI3K/Akt/mTOR and TGF-beta/Smad2/Smad3 signaling pathways were tested by western blot. IL33 administration was associated with the rebalance of Th1/Th2 and Tregs, as well as a superior suppressor activity of Tregs on effector T cells in sarcoidosis, probably through increasing ST2 expressions on Tregs, along with the suppression of PI3K/Akt/mTOR and TGF-beta/Smad2/Smad3 signaling pathways. Small dose of anti-IL23 antibody independently improved Th1/Th2 bias, but had limited effects on the homeostasis and ST2 expressions on Tregs. These results suggested a major anti-inflammatory ability of IL33 to ameliorate the disturbance of Th1/Th2 and Tregs in pulmonary sarcoidosis, and provided rationales for further strategies of targeting the IL33/ST2 signals in the treatment of pulmonary sarcoidosis.
Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population
INTERNATIONAL IMMUNOPHARMACOLOGY
Authors: Mei, Lijun; Huang, Chongya; Wang, Ajing; Zhang, Xian
Abstract
Purpose: This study aimed to explore the associations between polymorphisms of a very important pharmacogene, ADRB2, two inflammation-related genes, IL33 and IL2RB, and the risk of lung cancer. Methods: Six polymorphisms of ADRB2, IL33, and IL2RB were genotyped in 300 lung cancer patients and 300 healthy controls using MassARRAY. The relationship between genotypes and lung cancer risk was evaluated using chi-square tests. Results: The minor allele of rs1042711 was a risk allele for lung cancer, whereas the minor alleles of rs7025417 and rs5756523 had protective effects against lung cancer (p < 0.05). The CT genotype of rs1042711 and the GT genotype of rs1560642 were associated with increased risk of lung cancer, whereas the CC and AA genotypes of rs7025417 and the CT and CC genotypes of rs5756523 were associated with decreased disease risk (p < 0.05). Genetic model analysis shows that rs1042711 and rs1560642 were associated with increased risk of lung cancer; whereas rs7025417, rs5756523, and rs2284033 were associated with decreased disease risk (p < 0.05). Stratification analysis showed that rs1042711 and rs1560642 were associated with increased risk of lung cancer in nonsmokers and smokers, respectively, whereas rs7025417 and rs5756523 were associated with decreased disease risk in both subgroups (p < 0.05). Conclusion: Our results shed new light on the association between polymorphisms of ADRB2, 1L33, and IL2RB and the risk of lung cancer.