Journal article

IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia

Bingtai Lu, Ming Liu, Jun Wang, Huifeng Fan, Diyuan Yang, Li Zhang, Xiaoqiong Gu, Junli Nie, Zhenjun Chen, Alexandra J Corbett, Michael J Zhan, Shengbo Zhang, Vanessa L Bryant, Andrew M Lew, James McCluskey, Hai-bin Luo, Jun Cui, Yuxia Zhang, Yifan Zhan, Gen Lu

Mucosal Immunology | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Community-acquired pneumonia (CAP) contributes substantially to morbidity and mortality in children under the age of 5 years. In examining bronchoalveolar lavages (BALs) of children with CAP, we found that interleukin-17 (IL-17) production was significantly increased in severe CAP. Immune profiling showed that mucosal-associated invariant T (MAIT) cells from the BALs, but not blood, of CAP patients actively produced IL-17 (MAIT17). Single-cell RNA-sequencing revealed that MAIT17 resided in a BAL-resident PLZFhiCD103+ MAIT subset with high expression of hypoxia-inducible factor 1α (HIF-1α), reflecting the hypoxic state of the inflamed tissue. CAP BALs also contained a T-bet+ MAIT1 subset and ..

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Grants

Awarded by National Natural Science Foundation of China (NSFC)


Awarded by Science and Technology Program Project of Guangdong Province


Awarded by Guangzhou Women and Children's Medical Center


Awarded by Australian National Health & Medical Research Council


Awarded by Future Fellowship from the Australian Research Council


Funding Acknowledgements

This work was supported by National Natural Science Foundation of China (NSFC) (#31770978 and #91742109 to Y.X.Z.), Science and Technology Program Project of Guangdong Province (#2014A020212020 to G.L.), Guangzhou Women and Children's Medical Center (Startup Fund #5001-3001032 to Y.X.Z.; Postdoc Fund #5001-3001060 to B.T.L.; Postdoc Fund #5001-3001061 to M.L.) and the Australian National Health & Medical Research Council (#1105209, #1143976, #1037321, #1080321 to A.M.L.). A.J.C. is the recipient of a Future Fellowship from the Australian Research Council (#FT160100083). We thank Dr. Sidonia Eckle and Ms. Bronwyn Meehan (University of Melbourne) for the production of MR1 tetramers. We also thank the children, their guardians, and the nurses who made this work possible.