Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis
Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04978-2 |
| _version_ | 1827326370756165632 |
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| author | Jialing Fang Jun Lei Boxiao He Yankang Wu Peng Chen Zaiqiao Sun Ning Wu Yafei Huang Pengcheng Wei Lei Yin Yongshun Chen |
| author_facet | Jialing Fang Jun Lei Boxiao He Yankang Wu Peng Chen Zaiqiao Sun Ning Wu Yafei Huang Pengcheng Wei Lei Yin Yongshun Chen |
| author_sort | Jialing Fang |
| collection | DOAJ |
| description | Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade. |
| first_indexed | 2024-03-07T14:43:29Z |
| format | Article |
| id | doaj.art-36d6b28360534518916084c0cdbae9ae |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:43:29Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-36d6b28360534518916084c0cdbae9ae2024-03-05T20:06:32ZengBMCJournal of Translational Medicine1479-58762024-02-0122111510.1186/s12967-024-04978-2Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysisJialing Fang0Jun Lei1Boxiao He2Yankang Wu3Peng Chen4Zaiqiao Sun5Ning Wu6Yafei Huang7Pengcheng Wei8Lei Yin9Yongshun Chen10State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyTongji Medical College, Huazhong University of Science and TechnologySchool of Medicine, Guangxi UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan UniversityAbstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.https://doi.org/10.1186/s12967-024-04978-2Sc-RNA-seqTissue resident memory T cellIntestineT cell differentiationClinical cancer significance |
| spellingShingle | Jialing Fang Jun Lei Boxiao He Yankang Wu Peng Chen Zaiqiao Sun Ning Wu Yafei Huang Pengcheng Wei Lei Yin Yongshun Chen Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis Journal of Translational Medicine Sc-RNA-seq Tissue resident memory T cell Intestine T cell differentiation Clinical cancer significance |
| title | Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis |
| title_full | Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis |
| title_fullStr | Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis |
| title_full_unstemmed | Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis |
| title_short | Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis |
| title_sort | decoding the transcriptional heterogeneity differentiation lineage clinical significance in tissue resident memory cd8 t cell of the small intestine by single cell analysis |
| topic | Sc-RNA-seq Tissue resident memory T cell Intestine T cell differentiation Clinical cancer significance |
| url | https://doi.org/10.1186/s12967-024-04978-2 |
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