CD8+ tissue-resident memory T cells induce oral lichen planus erosion via cytokine network
Abstract
CD8+ tissue-resident memory T (CD8+ Trm) cells play key roles in many immune-inflammation-related diseases. However, their characteristics in the pathological process of oral lichen planus (OLP) remains unclear. Therefore, we investigated the function of CD8+ Trm cells in the process of OLP. By using single-cell RNA sequencing profiling and spatial transcriptomics, we revealed that CD8+ Trm cells were predominantly located in the lamina propria adjacent to the basement membrane and were significantly increased in patients with erosive oral lichen planus (EOLP) compared to those with non-erosive OLP (NEOLP). Furthermore, these cells displayed enhanced cytokine production, including IFN-γ, TNF-α, and IL17, in patients with EOLP. And our clinical cohort of 1-year follow-up was also supported the above results in RNA level and protein level. In conclusion, our study provided a novel molecular mechanism for triggering OLP erosion by CD8+ Trm cells to secrete multiple cytokines, and new insight into the pathological development of OLP.
Data availability
The data of this study, including scRNA-seq data, ST data, and bulk RNA-seq data are available in the Gene Expression Omnibus (GEO) database, accession numbers GSE213345, GSE213346 and GSE211630.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81730030)
- Qianming Chen
National Natural Science Foundation of China (81730030)
- Hao Xu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All individuals provided written informed consent and this study was supported by the Ethics Committee of West China Hospital of Stomatology Sichuan University [WCHSIRB-2019-167].
Copyright
© 2023, Qing et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,226
- views
-
- 237
- downloads
-
- 13
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Genetics and Genomics
Becker muscular dystrophy (BMD), an X-linked muscular dystrophy, is mostly caused by an in-frame deletion of Duchenne muscular dystrophy (DMD). BMD severity varies from asymptomatic to severe, associated with the genotype of DMD. However, the underlying mechanisms remain unclear. We established BMD mice carrying three representative exon deletions: ex45–48 del., ex45–47 del., and ex45–49 del. (d45–48, d45–47, and d45–49), with high frequencies and different severities in the human BMD hotspot. All three BMD mice showed muscle weakness, muscle degeneration, and fibrosis, but these changes appeared at different times for each exon deletion, consistent with the severities obtained by the natural history study of BMD. BMD mice showed site-specific muscle changes, unlike mdx mice, which showed diffuse muscle changes, and we demonstrated selective type IIa fiber reduction in BMD mice. Furthermore, BMD mice showed sarcolemmal neuronal nitric oxide synthase (nNOS) reduction and morphological capillary changes around type IIa fibers. These results suggest that capillary changes caused by nNOS reduction may be associated with the mechanism of skeletal muscle degeneration and type IIa fiber reduction in BMD mice. BMD mice may be useful in elucidating the pathomechanisms and developing vascular targeted therapies for human BMD.
-
- Genetics and Genomics
- Microbiology and Infectious Disease
Evolution of gene expression frequently drives antibiotic resistance in bacteria. We had previously (Patel and Matange, eLife, 2021) shown that, in Escherichia coli, mutations at the mgrB locus were beneficial under trimethoprim exposure and led to overexpression of dihydrofolate reductase (DHFR), encoded by the folA gene. Here, we show that DHFR levels are further enhanced by spontaneous duplication of a genomic segment encompassing folA and spanning hundreds of kilobases. This duplication was rare in wild-type E. coli. However, its frequency was elevated in a lon-knockout strain, altering the mutational landscape early during trimethoprim adaptation. We then exploit this system to investigate the relationship between trimethoprim pressure and folA copy number. During long-term evolution, folA duplications were frequently reversed. Reversal was slower under antibiotic pressure, first requiring the acquisition of point mutations in DHFR or its promoter. Unexpectedly, despite resistance-conferring point mutations, some populations under high trimethoprim pressure maintained folA duplication to compensate for low abundance DHFR mutants. We find that evolution of gene dosage depends on expression demand, which is generated by antibiotic and exacerbated by proteolysis of drug-resistant mutants of DHFR. We propose a novel role for proteostasis as a determinant of copy number evolution in antibiotic-resistant bacteria.