Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection

Flommersfeld, Sophie; Böttcher, Jan; Ersching, Jonatan; Floßdorf, Michael; Meiser, Philippa; Pachmayr, Ludwig O.; Leube, Justin; Hensel, Inge; Jarosch, Sebastian; Zhang, Qin; Chaudhry, M. Zeeshan; Andrae, Immanuel; Schiemann, Matthias; Busch, Dirk H.; Čičin‐Šain, Luka; Sun, Joseph C.; Gasteiger, Georg; Victora, Gabriel D.; Höfer, Thomas; Buchholz, Veit R.; Grassmann, Simon

doi:10.1016/j.immuni.2021.08.002

Cited by 54 publications

(50 citation statements)

References 49 publications

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“…Also, Gerein et al (34) found that RRP patients with HPV11 genotyping displayed a more aggressive disease course and a lower incidence of long-term response to IFN-alpha therapy (14% of HPV11 vs. 64% of HPV6). However, a recent study by Flommersfeld et al (35) provided evidence that ILC1-like NK cells are a transcriptionally, phenotypically, and functionally distinct NK cell lineage, but they seem to not derive from NK cytotoxic cells, but from an independent lineage (36); therefore, further studies are still needed to provide evidence that the E6 and E7 oncogenes of HPV11 virus facilitate tumor immunoevasion through TGF−b1-induced conversion of NK cells. In summary, our present studies demonstrate that low-risk infection might induce secretion of TGF−b1 by papillomatosis that leads to reduced NK cell cytotoxicity through downregulating NK cell-activating receptors and consequently facilitates low-risk HPV11 persistent infection in JORRP patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, a recent study by Flommersfeld et al. ( 35 ) provided evidence that ILC1-like NK cells are a transcriptionally, phenotypically, and functionally distinct NK cell lineage, but they seem to not derive from NK cytotoxic cells, but from an independent lineage ( 36 ); therefore, further studies are still needed to provide evidence that the E6 and E7 oncogenes of HPV11 virus facilitate tumor immunoevasion through TGF−β1-induced conversion of NK cells.…”

Section: Discussionmentioning

confidence: 99%

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Reduced NK Cell Cytotoxicity by Papillomatosis-Derived TGF-β Contributing to Low-Risk HPV Persistence in JORRP Patients

Xiao

Guo

et al. 2022

Front. Immunol.

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The role of natural killer (NK) cells in juvenile-onset recurrent respiratory papillomatosis (JORRP) patients remains elusive. In this study, we find increased NK cell percentage, particularly CD11b-CD27- (DN) subsets in peripheral blood of JORRP patients and associated with disease activity. RNA sequencing shows a downregulated “natural killer cell-mediated cytotoxicity” feature in JORRP tumors. We also find impaired cytotoxic capacity and lower expression of NK cell-activating receptors including NKp30 and NKp46. Higher transforming growth factor-beta 1 (TGF-β1) is found both in plasma and tumor tissues of JORRP, and anti-TGF-β1 antibody could restore NK cell cytolytic activity and upregulate NKp30 and NKG2D expression. Also, we find a significantly higher Chemokine receptor type 6 (CXCR6) on NK cells in tumors compared with that in peripheral blood. Finally, RT-PCR analysis show that both HPV6-E6-E7 and HPV11-E6-E7 overexpression leads to higher TGFB1 expression compared with control SNU-1076 cell line, and higher CXCR6 expression is detected on NK coculture with HPV11-E6-E7-overexpressing cells. In conclusion, we demonstrate that TGF-β1 by papillomatosis leads to decreased NK cell cytotoxicity through downregulating NK cell-activating receptors in JORRP patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduced NK Cell Cytotoxicity by Papillomatosis-Derived TGF-β Contributing to Low-Risk HPV Persistence in JORRP Patients

Xiao

Guo

et al. 2022

Front. Immunol.

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“…Interestingly, recent evidence in murine models shows that CD160 -ILC1 exhibit cytotoxicity against YAC-1 cells (22). In addition, certain populations of splenic ILC1-like NK cells are able to kill cells infected with murine cytomegalovirus (3,18,22,39). NK cells play a special role in antitumor surveillance and in antimicrobial defense against intracellular pathogens and viruses (39).…”

Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells in Autoimmune Diseases

et al. 2022

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Innate lymphoid cells (ILC) are a heterogeneous group of immune cells characterized by lymphoid morphology and cytokine profile similar to T cells but which do not express clonally distributed diverse antigen receptors. These particular cells express transcription factors and cytokines reflecting their similarities to T helper (Th)1, Th2, and Th17 cells and are therefore referred to as ILC1, ILC2, and ILC3. Other members of the ILC subsets include lymphoid tissue inducer (LTi) and regulatory ILC (ILCreg). Natural killer (NK) cells share a common progenitor with ILC and also exhibit a lymphoid phenotype without antigen specificity. ILC are found in low numbers in peripheral blood but are much more abundant at barrier sites such as the skin, liver, airways, lymph nodes, and the gastrointestinal tract. They play an important role in innate immunity due to their capacity to respond rapidly to pathogens through the production of cytokines. Recent evidence has shown that ILC also play a key role in autoimmunity, as alterations in their number or function have been identified in systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Here, we review recent advances in the understanding of the role of ILC in the pathogenesis of autoimmune diseases, with particular emphasis on their role as a potential diagnostic biomarker and as therapeutic targets.

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“…These data additionally augment previous evidence that human NK-DC interactions enhance DC cross-presentation of tumor antigens and provide further mechanistic insight within the TME ( 117 ). Furthermore, specific ILC subtypes may preferentially interact with DCs, as a recent study identified a group of ILC1-like NK cells characterized as CD27 + CD62L - CD160 + virus-responsive Ly49H + NK cells during mouse CMV (MCMV) infection ( 118 ). These cells exhibited transcriptional and functional signatures of both ILC1s and NK cells but interestingly were also marked by high expression of Batf3 and XCL1.…”

Section: Introductionmentioning

confidence: 99%

Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function

O’Sullivan

2022

Front. Immunol.

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NK cells play a crucial role in host protection during tumorigenesis. Throughout tumor development, however, NK cells become progressively dysfunctional through a combination of dynamic tissue-specific and systemic factors. While a number of immunosuppressive mechanisms present within the tumor microenvironment have been characterized, few studies have contextualized the spatiotemporal dynamics of these mechanisms during disease progression and across anatomical sites. Understanding how NK cell immunosuppression evolves in these contexts will be necessary to optimize NK cell therapy for solid and metastatic cancers. Here, we outline the spatiotemporal determinants of antitumor NK cell regulation, including heterogeneous tumor architecture, temporal disease states, diverse cellular communities, as well as the complex changes in NK cell states produced by the sum of these higher-order elements. Understanding of the signals encountered by NK cells across time and space may reveal new therapeutic targets to harness the full potential of NK cell therapy for cancer.

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Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection

Cited by 54 publications

References 49 publications

Reduced NK Cell Cytotoxicity by Papillomatosis-Derived TGF-β Contributing to Low-Risk HPV Persistence in JORRP Patients

Reduced NK Cell Cytotoxicity by Papillomatosis-Derived TGF-β Contributing to Low-Risk HPV Persistence in JORRP Patients

Innate Lymphoid Cells in Autoimmune Diseases

Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function

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