Iranian Journal of Allergy, Asthma and Immunology 2017. 16(6):511-519.

Imbalance of Th17/Treg in the Pathogenesis of Mice with Paraquat-induced Acute Lung Injury
Xia Yang, Jing-Hong Zhang, Jian-Feng Zhang, Hua Lin, Wei Chen, Li Xiang, Chao-Qian Li


Recent studies suggest that imbalances in the ratios of CD4+ T helper cell subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment. Hematoxylin-eosin and TUNEL staining procedures were performed to examine inflammation and apoptosis. The presence of Th17 and Treg cells was measured by flow cytometry; the expression of putative Th17 cytokines and transcription factors was measured by ELISA and western blot analysis. Compared with control mice, lung inflammation and apoptosis were dramatically increased in PQP mice at 12 and 24 hours after poisoning. In addition, poisoned mice displayed significant increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of IL-17A and IL-17, as measured by flow cytometry and western blot assays. This increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg) and in the expression of IL-35 and the transcription factor Foxp3. These results suggest that an imbalanced ratio of Th17/Treg cells may contribute to the pathogenesis of PQ-induced ALI.


Acute lung injury; Paraquat; Poisoning; Th17/Treg imbalance

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1. Kanchan T, Bakkannavar SM, Acharya PR. Paraquat Poisoning: Analysis of an Uncommon cause of Fatal Poisoning from Manipal, South India. ToxicolInt2015; 22(1):30-4.

2. Yu HJ, Fang Q. Clinical data analysis of severe acute paraquat poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2010; 28(10):786-7.

3. Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol 2011; 72(5):745-57.

4. Chen JG, Eldridge DL, Lodeserto FJ, Ming DY, Turner KM, Vanderford JL, et al. Paraquat ingestion: a challenging diagnosis. Pediatrics 2010; 125(6):e1505-9.

5. Yu G, Kan B, Jian X, Wang J, Sun J, Song C. A case report of acute severe paraquat poisoning and long-term follow-up. Exp Ther Med 2014; 8(1):233-6.

6. Nakajima T, Lin KW, Li J, McGee HS,Kwan JM,Perkins DL, et al. T cells and lung injury. Impact of rapamycin. Am J Respir Cell Mol Biol 2014; 51(2):294-9.

7. Esmaeil M, Fatemeh R, Davar A, Arda K, Johan G,Ian M. A, et al. The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis. Iran J Allergy Asthma Immunol 2016; 15(4):334-9.

8. Zhang JG, Chen XJ, Liu T, Jiang SJ. FOXP3+ associated with the pro-inflammatory regulatory T and T helper 17 effector cells in asthma patients. Exp Ther Med 2016; 12(4):2753-8.

9. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med 2009; 361(9):888-98.

10. Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional Specialization of Interleukin-17 Family members. Immunity 2011; 34(2):149-62.

11. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4(4):330-6.

12. Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 2014; 13(6):668-77.

13. Zhang F, Li MY, Lan YY, Wang CB. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury. Sci Rep 2016; 6(2):21348.

14. Yu ZX, Ji MS, Yan J, Cai Y, Liu J, Yang HF, et al. The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome. Crit Care 2015; 19:82.

15. Zhang J, Li C, Guo S. Effects of inhaled inactivated Mycobacterium phlei on airway inflammation in mouse asthmatic models. J Aerosol Med Pulm Drug Deliv 2012; 25(2):96-103.

16. Yang C, Song HW, Liu W, Dong XS, Liu Z. Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice. Inflammation. 2017 Sep 22.

17. Ren M, Wang YM, Zhao J, Zhao J, Zhao ZM, Zhang TF, et al. Metallothioneins attenuate paraquat-induced acute lung injury in mice through the mechanisms of anti-oxidation and anti-apoptosis. Food Chem Toxicol 2014; 73:140-7.

18. Liu W, Shan LP, Dong XS, Liu Z. Toll-like receptor 4 implicated in acute lung injury induced by paraquat poisoning in mice. Int J Clin Exp Med 2014; 7(10):3392-7.

19. Guo H, He Z, Li M, Wang T, Zhang L. Imbalance of peripheral blood Th17 and Treg responses in children with refractory Mycoplasma pneumoniae pneumonia. J Infect Chemother 2016; 22(3):162-6.

20. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunology 2010; 40(7):1830-5.

21. Whitehead GS, Wilson RH, Nakano K,Burch LH, Nakano H, Cook DN.IL-35 production by inducible costimulator (ICOS)-positive regulatory T cells reverses established IL-17-dependent allergic airways disease. J Allergy Clin Immunol 2012; 129(1):207-15.e1-5.

22. Cosmi L, Maggi L, Santarlasci V, Liotta F, Annunziato F. T helper cells plasticity in inflammation. Cytometry A 2014; 85(1):36-42.

23. Jadidi-Niaragh F, Mirshafiey A. The deviated balance between regulatory T cell and Th17 in autoimmunity. ImmunopharmacolImmunotoxicol2012; 34(5):727-39.

24. Ma L, Xue HB, Guan XH, Shu CM, Wang F, Zhang JH,et al. The Imbalance of Th17 cells and CD4(+) CD25(high) Foxp3(+) Treg cells in patients with atopic dermatitis. J Eur Acad Dermatol Venereol 2014; 28(8):1079-86.

25. Zhang F, Li M, Lan Y, Wang C. Imbalcance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury. Sci Rep. 2016; 6: 21348.


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