IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
| Autor: | Gen Lu, James McCluskey, Hai-Bin Luo, Shengbo Zhang, Diyuan Yang, Ming Liu, Yuxia Zhang, Alexandra J. Corbett, Andrew M. Lew, Yifan Zhan, Jun Cui, Michael J Zhan, Junli Nie, Jun Wang, Vanessa L. Bryant, Li Zhang, Xiaoqiong Gu, Bingtai Lu, Huifeng Fan, Zhenjun Chen |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Immunology Inflammation Mucosal associated invariant T cell Lymphocyte Activation Article Monocytes Mucosal-Associated Invariant T Cells Immunophenotyping Transcriptome Mice 03 medical and health sciences 0302 clinical medicine T-Lymphocyte Subsets Animals Humans Immunology and Allergy Medicine Child Receptor business.industry Gene Expression Profiling Interleukin-17 Pneumonia medicine.disease Gene expression profiling Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Cytokines Th17 Cells Female Disease Susceptibility Interleukin 17 Inflammation Mediators medicine.symptom business Biomarkers Transcription Factors |
| Zdroj: | Mucosal Immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/s41385-020-0273-y |
| Popis: | 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 a novel DDIT3+ (DNA damage-inducible transcript 3-positive) MAIT subset with low expression of HIF1A. Furthermore, MAIT17 differed from T-helper type 17 (Th17) cells in the expression of genes related to tissue location, innateness, and cytotoxicity. Finally, we showed that BAL monocytes were hyper-inflammatory and elicited differentiation of MAIT17. Thus, tissue-resident MAIT17 cells are induced at the infected respiratory mucosa, likely influenced by inflammatory monocytes, and contribute to IL-17-mediated inflammation during CAP. |
| Databáze: | OpenAIRE |
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