NK cells and type 1 innate lymphoid cells: partners in host defense

Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1) are specific innate lymphoid cell subsets that are key for the detection and elimination of pathogens and cancer cells. In liver, while they share a number of characteristics, they differ in many features. These include their developmental pathways, tissue distribution, phenotype and functions. NK cells and ILC1 contribute to organ homeostasis through the production of key cytokines and chemokines and the elimination of potential harmful bacteria and viruses. In addition, they are equipped with a wide range of receptors, allowing them to detect “stressed cells’ such as cancer cells. Our understanding of the role of innate lymphoid cells in hepatocellular carcinoma (HCC) is growing owing to the development of mouse models, the progress in immunotherapeutic treatment and the recent use of scRNA sequencing analyses. In this review, we summarize the current understanding of NK cells and ILC1 in hepatocellular carcinoma and discuss future strategies to take advantage of these innate immune cells in anti-tumor immunity. Immunotherapies hold great promise in HCC, and a better understanding of the role and function of NK cells and ILC1 in liver cancer could pave the way for new NK cell and/or ILC1-targeted treatment.

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Hobit confers tissue-dependent programs to type 1 innate lymphoid cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2117965118 ◽

2021 ◽

Vol 118 (50) ◽

pp. e2117965118

Author(s):

Kentaro Yomogida ◽

Tarin M. Bigley ◽

Tihana Trsan ◽

Susan Gilfillan ◽

Marina Cella ◽

...

Keyword(s):

Viral Infection ◽

Nk Cells ◽

Salivary Glands ◽

Intestinal Mucosa ◽

Nk Cell ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Unique Cell ◽

The Impact

Identification of type 1 innate lymphoid cells (ILC1s) has been problematic. The transcription factor Hobit encoded by Zfp683 has been proposed as a major driver of ILC1 programs. Using Zfp683 reporter mice, we showed that correlation of Hobit expression with ILC1s is tissue- and context-dependent. In liver and intestinal mucosa, Zfp683 expression correlated well with ILC1s; in salivary glands, Zfp683 was coexpressed with the natural killer (NK) master transcription factors Eomes and TCF1 in a unique cell population, which we call ILC1-like NK cells; during viral infection, Zfp683 was induced in conventional NK cells of spleen and liver. The impact of Zfp683 deletion on ILC1s and NK cells was also multifaceted, including a marked decrease in granzyme- and interferon-gamma (IFNγ)–producing ILC1s in the liver, slightly fewer ILC1s and more Eomes+ TCF1+ ILC1-like NK cells in salivary glands, and only reduced production of granzyme B by ILC1 in the intestinal mucosa. NK cell–mediated control of viral infection was unaffected. We conclude that Hobit has two major impacts on ILC1s: It sustains liver ILC1 numbers, while promoting ILC1 functional maturation in other tissues by controlling TCF1, Eomes, and granzyme expression.

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Faculty Opinions recommendation of Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717971086.793469559 ◽

2013 ◽

Author(s):

Booki Min

Keyword(s):

Fungal Infection ◽

Host Defense ◽

Innate Lymphoid Cells ◽

Cutting Edge ◽

Lymphoid Cells

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Faculty Opinions recommendation of S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732403307.793543457 ◽

2018 ◽

Author(s):

Dan Conrad

Keyword(s):

Host Defense ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Group 2

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The role of donor‐unrestricted T‐cells, innate lymphoid cells, and NK cells in anti‐mycobacterial immunity

Immunological Reviews ◽

10.1111/imr.12948 ◽

2021 ◽

Author(s):

Paula Ruibal ◽

Linda Voogd ◽

Simone A. Joosten ◽

Tom H. M. Ottenhoff

Keyword(s):

T Cells ◽

Nk Cells ◽

Innate Lymphoid Cells ◽

Lymphoid Cells

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Transcriptional regulatory networks that promote and restrict identities and functions of intestinal innate lymphoid cells

10.1101/465435 ◽

2018 ◽

Cited By ~ 1

Author(s):

Maria Pokrovskii ◽

Jason A. Hall ◽

David E. Ochayon ◽

Ren Yi ◽

Natalia S. Chaimowitz ◽

...

Keyword(s):

Regulatory Networks ◽

Inflammatory Diseases ◽

Innate Lymphoid Cells ◽

Chromatin Accessibility ◽

Immune Defense ◽

Lymphoid Cells ◽

Transcriptional Regulatory Networks ◽

Transcriptional Regulatory

SummaryInnate lymphoid cells (ILCs) can be subdivided into several distinct cytokine-secreting lineages that promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. Accumulating evidence suggests that ILCs, similarly to other immune populations, are capable of phenotypic and functional plasticity in response to infectious or environmental stimuli. Yet the transcriptional circuits that control ILC identity and function are largely unknown. Here we integrate gene expression and chromatin accessibility data to infer transcriptional regulatory networks within intestinal type 1, 2, and 3 ILCs. We predict the “core” sets of transcription-factor (TF) regulators driving each ILC subset identity, among which only a few TFs were previously known. To assist in the interpretation of these networks, TFs were organized into cooperative clusters, or modules that control gene programs with distinct functions. The ILC network reveals extensive alternative-lineage-gene repression, whose regulation may explain reported plasticity between ILC subsets. We validate new roles for c-MAF and BCL6 as regulators affecting the type 1 and type 3 ILC lineages. Manipulation of TF pathways identified here might provide a novel means to selectively regulate ILC effector functions to alleviate inflammatory disease or enhance host tolerance to pathogenic microbes or noxious stimuli. Our results will enable further exploration of ILC biology, while our network approach will be broadly applicable to identifying key cell state regulators in otherin vivocell populations.

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