Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner

Koh, June-Young; Rha, Min‐Seok; Choi, Seong Jin; Lee, Ha Seok; Han, Jiwon; Nam, Heejin; Kim, Dong-Uk; Lee, Jae Geun; Kim, Myoung Soo; Park, Jun Yong; Park, Su–Hyung; Joo, Dong Jin; Shin, Eui‐Cheol

doi:10.1016/j.jhep.2022.05.020

Cited by 19 publications

(12 citation statements)

References 67 publications

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“…CD8 + Effector Memory T cells (CD8 EM ) were distinguished by low/absent CD27, increased S1PR1 expression, and persistently high expression of the effector molecules PRF1 and GZMB (51, 52). Recently, a CD56 + CD161 - NK-like CD8 + T cell subpopulation in the liver was described, which is present in the sinusoids, bears some tissue residence markers including CD69 and CD103, has a restricted TCR repertoire, and is characterized by increased expression of NK markers including NCAM1 and KLRC2 (47). We uncovered a very similar population in our intragraft single cell analysis, identifying a subpopulation of CD8 + T cells expressing NCAM1, KLRC1/C2 , and KLRD1 but lacking expression of Eomes and CD161/KLRB1 ( Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution

Peters,

DePasquale,

Begum

et al. 2024

Preprint

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Acute cellular rejection (ACR) affects >80% of pediatric liver transplant recipients within 5 years, and late ACR is associated with graft failure. Traditional anti-rejection therapy for late ACR is ineffective and has remained unchanged for six decades. Although CD8+ T cells promote late ACR, little has been done to define their specificity and gene expression. Here, we used single-cell sequencing and immune repertoire profiling (10X Genomics) on 30 cryopreserved 16G liver biopsies from 14 patients (5 pre-transplant or with no ACR, 9 with ACR). We identified expanded intragraft CD8+ T cell clonotypes (CD8EXP) and their gene expression profiles in response to anti-rejection treatment. Notably, we found that expanded CD8+ clonotypes (CD8EXP) bore markers of effector and CD56hiCD161- 'NK-like' T cells, retaining their clonotype identity and phenotype in subsequent biopsies from the same patients despite histologic ACR resolution. CD8EXP clonotypes localized to portal infiltrates during active ACR, and persisted in the lobule after histologic ACR resolution. CellPhoneDB analysis revealed differential crosstalk between KC and CD8EXP during late ACR, with activation of the LTB-LTBR pathway and downregulation of TGFβ signaling. Therefore, persistently-detected intragraft CD8EXP clones remain active despite ACR treatment and may contribute to long-term allograft fibrosis and failure of operational tolerance.

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Section: Resultsmentioning

confidence: 99%

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution

Peters,

DePasquale,

Begum

et al. 2024

Preprint

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“…95 PolyA Paired CD45RA-CD4 + T GepLiver-sc-08 GSE186343 96 N/A PolyA Paired N/A GepLiver-sc-09 GSE200173 Koh, J. Y. et al . 37 PolyA Paired CD45+ GepLiver-sc-10 GSE136103 Ramachandran, P et al . 10 PolyA Paired CD45 +/− GepLiver-sc-11 GSE168933 Buonomo, E. L. et al .…”

Section: Methodsmentioning

confidence: 99%

GepLiver: an integrative liver expression atlas spanning developmental stages and liver disease phases

Zhang

Qin

et al. 2023

Sci Data

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Chronic liver diseases usually developed through stepwise pathological transitions under the persistent risk factors. The molecular changes during liver transitions are pivotal to improve liver diagnostics and therapeutics yet still remain elusive. Cumulative large-scale liver transcriptomic studies have been revealing molecular landscape of various liver conditions at bulk and single-cell resolution, however, neither single experiment nor databases enabled thorough investigations of transcriptomic dynamics along the progression of liver diseases. Here we establish GepLiver, a longitudinal and multidimensional liver expression atlas integrating expression profiles of 2469 human bulk tissues, 492 mouse samples, 409,775 single cells from 347 human samples and 27 liver cell lines spanning 16 liver phenotypes with uniformed processing and annotating methods. Using GepLiver, we have demonstrated dynamic changes of gene expression, cell abundance and crosstalk harboring meaningful biological associations. GepLiver can be applied to explore the evolving expression patterns and transcriptomic features for genes and cell types respectively among liver phenotypes, assisting the investigation of liver transcriptomic dynamics and informing biomarkers and targets for liver diseases.

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“…and activating receptors such as NKG2D. 85 It is therefore reasonable to speculate that the progenitor of human αβILTCKs with attenuated TCR signaling likely underwent agonist selection. Indeed, recent observations in human postnatal thymocytes highlighted a population of αβ lineage CD8 + PD-1 + CD10 + T cells that evince a history of agonist selection including upregulation of CD8αα and suppression of CCR7 and CD62L, molecules involved in T-cell homing to secondary lymphoid organs.…”

Section: Tissue-resident Killer Innate-like T-cell Response In Human ...mentioning

confidence: 99%

“…In melanoma, αβILTCK‐like T cells that display an NK‐like tissue‐resident phenotype also expand in tumors 84 . In hepatocellular carcinoma, αβILTCK‐like T cells are induced and express the innate lymphocyte marker CD56 and HOBIT, a tissue residency‐promoting transcription factor that likely drives their high expression of CD49a, CD103, CD69, and CXCR6 85 . Additionally, these cells evoke functional hallmarks of αβILTCKs including hyporesponsiveness to TCR stimulation in favor of activation through cytokines including IL‐15 and activating receptors such as NKG2D 85 …”

Section: Tissue‐resident Cytotoxic Innate Lymphocyte and Killer Innat...mentioning

confidence: 99%

Cancer immunity by tissue‐resident type 1 innate lymphoid cells and killer innate‐like T cells

Zhang,

Li,

Kansler

et al. 2024

Immunological Reviews

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SummaryCancer progression can be restrained by tumor‐infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre‐wired, in which innate lymphocytes and innate‐like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming‐dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming‐dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell‐directed therapeutic programs, recent studies have revealed that pre‐wired cancer immunity mediated by tissue‐resident type 1 innate lymphoid cells (ILC1s) and killer innate‐like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer‐sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed.

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Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner

Cited by 19 publications

References 67 publications

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution

GepLiver: an integrative liver expression atlas spanning developmental stages and liver disease phases

Cancer immunity by tissue‐resident type 1 innate lymphoid cells and killer innate‐like T cells

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