Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells
Human lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study, we performed RNA sequencing on the three NK cell p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01829/full |
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| author | Janine E. Melsen Gertjan Lugthart Carly Vervat Szymon M. Kielbasa Sander A. J. van der Zeeuw Henk P. J. Buermans Monique M. van Ostaijen-ten Dam Arjan C. Lankester Marco W. Schilham |
| author_facet | Janine E. Melsen Gertjan Lugthart Carly Vervat Szymon M. Kielbasa Sander A. J. van der Zeeuw Henk P. J. Buermans Monique M. van Ostaijen-ten Dam Arjan C. Lankester Marco W. Schilham |
| author_sort | Janine E. Melsen |
| collection | DOAJ |
| description | Human lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study, we performed RNA sequencing on the three NK cell populations derived from bone marrow (BM) and blood. In ltNK cells, 1,353 genes were differentially expressed compared to circulating NK cells. Several molecules involved in migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow cytometry we confirmed that the expression profile of adhesion molecules (CD49e−, CD29low, CD81high, CD62L−, CD11c−) and transcription factors (Eomeshigh, Tbetlow) of ltNK cells differed from their circulating counterparts. LtNK cells were characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their proliferative capacity was reduced compared to the circulating NK cells. By performing gene set enrichment analysis, we identified DUSP6 and EGR2 as potential regulators of the ltNK cell transcriptome. Remarkably, comparison of the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in BM. Together, we provide transcriptional and phenotypic data that clearly distinguish ltNK cells from both the CD56bright and CD56dim NK cells and substantiate the view that ltNK cells are tissue-resident cells, which are functionally restrained in killing and have low proliferative activity. |
| first_indexed | 2024-12-21T15:10:49Z |
| format | Article |
| id | doaj.art-2ca12db5370f4d2dbef63454458238cd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T15:10:49Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2ca12db5370f4d2dbef63454458238cd2022-12-21T18:59:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01829407315Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T CellsJanine E. Melsen0Gertjan Lugthart1Carly Vervat2Szymon M. Kielbasa3Sander A. J. van der Zeeuw4Henk P. J. Buermans5Monique M. van Ostaijen-ten Dam6Arjan C. Lankester7Marco W. Schilham8Department of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Biomedical Data Sciences, Leiden University Medical Center, Leiden, NetherlandsDepartment of Biomedical Data Sciences, Leiden University Medical Center, Leiden, NetherlandsDepartment of Human Genetics, Leiden Genome Technology Center, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pediatrics, Leiden University Medical Center, Leiden, NetherlandsHuman lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study, we performed RNA sequencing on the three NK cell populations derived from bone marrow (BM) and blood. In ltNK cells, 1,353 genes were differentially expressed compared to circulating NK cells. Several molecules involved in migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow cytometry we confirmed that the expression profile of adhesion molecules (CD49e−, CD29low, CD81high, CD62L−, CD11c−) and transcription factors (Eomeshigh, Tbetlow) of ltNK cells differed from their circulating counterparts. LtNK cells were characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their proliferative capacity was reduced compared to the circulating NK cells. By performing gene set enrichment analysis, we identified DUSP6 and EGR2 as potential regulators of the ltNK cell transcriptome. Remarkably, comparison of the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in BM. Together, we provide transcriptional and phenotypic data that clearly distinguish ltNK cells from both the CD56bright and CD56dim NK cells and substantiate the view that ltNK cells are tissue-resident cells, which are functionally restrained in killing and have low proliferative activity.https://www.frontiersin.org/article/10.3389/fimmu.2018.01829/fullnatural killer cellstissue-residentRNA sequenceCD8+ T cellslymphoid tissue |
| spellingShingle | Janine E. Melsen Gertjan Lugthart Carly Vervat Szymon M. Kielbasa Sander A. J. van der Zeeuw Henk P. J. Buermans Monique M. van Ostaijen-ten Dam Arjan C. Lankester Marco W. Schilham Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells Frontiers in Immunology natural killer cells tissue-resident RNA sequence CD8+ T cells lymphoid tissue |
| title | Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells |
| title_full | Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells |
| title_fullStr | Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells |
| title_full_unstemmed | Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells |
| title_short | Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8+ T Cells |
| title_sort | human bone marrow resident natural killer cells have a unique transcriptional profile and resemble resident memory cd8 t cells |
| topic | natural killer cells tissue-resident RNA sequence CD8+ T cells lymphoid tissue |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01829/full |
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