Comparative analysis reveals a role for TGF-β in shaping the residency-related transcriptional signature in tissue-resident memory CD8+ T cells

• Published in: PloS one Vol. 14; no. 2; p. e0210495
• Main Authors: Nath, Artika P, Braun, Asolina, Ritchie, Scott C, Carbone, Francis R, Mackay, Laura K, Gebhardt, Thomas, Inouye, Michael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.02.2019; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Comparative analysis; Cytokines; Diabetes; Female; Flow cytometry; Gene Expression Regulation; Gene set enrichment analysis; Genomes; Genomic imprinting; Genomics; Growth factors; Immune system; Immunologic Memory; Immunological memory; Immunology; Imprinting; Infections; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Memory cells; Mice, Inbred C57BL; Primary care; Public health; Research and Analysis Methods; Ribonucleic acid; RNA; Signaling; Signatures; T cell receptors; Tissues; Transcription; Transcriptome; Transforming growth factor; Transforming Growth Factor beta - immunology; Transforming growth factor-b; United Kingdom > UK; Australia; Victoria Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0210495

Tissue-resident CD8+ memory T (TRM) cells are immune cells that permanently reside at tissue sites where they play an important role in providing rapid protection against reinfection. They are not only phenotypically and functionally distinct from their circulating memory counterparts, but also exhibit a unique transcriptional profile. To date, the local tissue signals required for their development and long-term residency are not well understood. So far, the best-characterised tissue-derived signal is transforming growth factor-β (TGF-β), which has been shown to promote the development of these cells within tissues. In this study, we aimed to determine to what extent the transcriptional signatures of TRM cells from multiple tissues reflects TGF-β imprinting. We activated murine CD8+ T cells, stimulated them in vitro by TGF-β, and profiled their transcriptomes using RNA-seq. Upon comparison, we identified a TGF-β-induced signature of differentially expressed genes between TGF-β-stimulated and -unstimulated cells. Next, we linked this in vitro TGF-β-induced signature to a previously identified in vivo TRM-specific gene set and found considerable (>50%) overlap between the two gene sets, thus showing that a substantial part of the TRM signature can be attributed to TGF-β signalling. Finally, gene set enrichment analysis further revealed that the altered gene signature following TGF-β exposure reflected transcriptional signatures found in TRM cells from both epithelial and non-epithelial tissues. In summary, these findings show that TGF-β has a broad footprint in establishing the residency-specific transcriptional profile of TRM cells, which is detectable in TRM cells from diverse tissues. They further suggest that constitutive TGF-β signaling might be involved for their long-term persistence at tissue sites.