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Int J Med Sci 2017; 14(10):977-983. doi:10.7150/ijms.20212 This issue Cite

Research Paper

IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis

Hao Wang1, Jingdong Li2, Qiyang Han3, Fei Yang4, Yu Xiao5, Meng Xiao6, Yingchun Xu6, Longxiang Su1, Na Cui1✉, Dawei Liu1✉

1. Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China;
2. Department of Critical Care Medicine, 4 th Peoples' Hospital of Shenyang, Liaoning Province, China;
3. Department of Critical Care Medicine, Dalizhou People's Hospital, Yunnan Province, China;
4. Department of Critical Care Medicine, Chifeng City Hospital, Inner Mongolia, China;
5. Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science;
6. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science.

✉ Corresponding authors: Na Cui, Tel: +86 15601212623, Email: cuinacn Dawei Liu, Tel: +86 10 69152300, Email: pumchkycncom Department of Critical Care Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, More

Citation:
Wang H, Li J, Han Q, Yang F, Xiao Y, Xiao M, Xu Y, Su L, Cui N, Liu D. IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis. Int J Med Sci 2017; 14(10):977-983. doi:10.7150/ijms.20212. https://www.medsci.org/v14p0977.htm
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Abstract

Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8+ T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure.

Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. The blood samples were obtained before the mice sacrificed and lung specimens were taken. Pathological sections were stained with hematoxylin and eosin (HE). The number of CD8+effective memory T cells (Tem) and the expression of IFN-γ, mTOR, ribosomal protein S6 kinase (S6K), T-bet and EOMES were measured by flow cytometry. The levels of IL-6, IL-10 and Galactomannan (GM) were determined by ELISA.

Results: After IL-12 treatment, the number of CD8+ Tem and the expression of IFN-γ increased significantly; while quite the opposite results were observed when the mTOR pathway was blocked by rapamycin. The expression of mTOR and S6K as well as the level of IFN-γ of the IL-12 treatment group were significantly higher than those in IPA and IPA + rapamycin groups. In addition, IL-12 promoted increasing T-bet and down regulating Eomes to make the Tem transformation. The final immune effector was high level of inflammatory cytokines (IL-6) and low level of anti-inflammatory factors (IL-10) and this strengthened immune response to the Aspergillus infection.

Conclusions: The biological effects of Tem could significantly affect IPA infection host immune regulation, which depended on the activation of mTOR signaling pathway by IL-12.

Keywords: IL-12, Mammalian target of rapamycin (mTOR), CD8+effect memory T cells (Tem), Invasive Pulmonary Aspergillosis (IPA).

Citation styles

APA
Wang, H., Li, J., Han, Q., Yang, F., Xiao, Y., Xiao, M., Xu, Y., Su, L., Cui, N., Liu, D. (2017). IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis. International Journal of Medical Sciences, 14(10), 977-983. https://doi.org/10.7150/ijms.20212.

ACS
Wang, H.; Li, J.; Han, Q.; Yang, F.; Xiao, Y.; Xiao, M.; Xu, Y.; Su, L.; Cui, N.; Liu, D. IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis. Int. J. Med. Sci. 2017, 14 (10), 977-983. DOI: 10.7150/ijms.20212.

NLM
Wang H, Li J, Han Q, Yang F, Xiao Y, Xiao M, Xu Y, Su L, Cui N, Liu D. IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis. Int J Med Sci 2017; 14(10):977-983. doi:10.7150/ijms.20212. https://www.medsci.org/v14p0977.htm

CSE
Wang H, Li J, Han Q, Yang F, Xiao Y, Xiao M, Xu Y, Su L, Cui N, Liu D. 2017. IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis. Int J Med Sci. 14(10):977-983.

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