دورية أكاديمية
Integrated single-cell transcriptome and T cell receptor profiling reveals defects of T cell exhaustion in pulmonary tuberculosis.
| العنوان: | Integrated single-cell transcriptome and T cell receptor profiling reveals defects of T cell exhaustion in pulmonary tuberculosis. |
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| المؤلفون: | Wen Z; Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Wang L; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Ma H; Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Li L; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Wan L; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Shi L; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Li H; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Chen H; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Hao W; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Song S; Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Xue Q; Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Wei Y; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Li F; Department of Respiratory Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Xu J; Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Zhang S; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China., Wong KW; Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: kwwong@gmail.com., Song Y; Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: yanzhengsong@163.com. |
| المصدر: | The Journal of infection [J Infect] 2024 Jun; Vol. 88 (6), pp. 106158. Date of Electronic Publication: 2024 Apr 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: W.B. Saunders Country of Publication: England NLM ID: 7908424 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2742 (Electronic) Linking ISSN: 01634453 NLM ISO Abbreviation: J Infect Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Kent, UK : W.B. Saunders Original Publication: London, New York, Academic Press. |
| مواضيع طبية MeSH: | Tuberculosis, Pulmonary*/immunology , Receptors, Antigen, T-Cell*/genetics , Receptors, Antigen, T-Cell*/metabolism , Receptors, Antigen, T-Cell*/immunology , CD8-Positive T-Lymphocytes*/immunology , Transcriptome* , Single-Cell Analysis* , CD4-Positive T-Lymphocytes*/immunology, Humans ; Lung/immunology ; Lung/pathology ; Male ; Female ; Mycobacterium tuberculosis/immunology ; Adult ; Middle Aged ; Gene Expression Profiling ; T-Cell Exhaustion |
| مستخلص: | Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: Chronic inflammation; Immunotherapy; Single-cell RNA sequencing; T cell exhaustion; Tuberculosis |
| تواريخ الأحداث: | Date Created: 20240420 Date Completed: 20240519 Latest Revision: 20240519 |
| رمز التحديث: | 20240520 |
| DOI: | 10.1016/j.jinf.2024.106158 |
| PMID: | 38642678 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1532-2742 |
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| DOI: | 10.1016/j.jinf.2024.106158 |