Details for: CL0001079

Cell ID: CL0001079

Cell Name: NKp44-positive group 3 innate lymphoid cell, human

Description: A group 3 innate lymphoid cell in the human with the phenotype IL-7Ralpha-positive, and NKp44-positive.

Selected Context(s): Overall

Gene Significance Landscape

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Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for NKp44-positive group 3 innate lymphoid cell, human within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for NKp44-positive group 3 innate lymphoid cell, human. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for NKp44-positive group 3 innate lymphoid cell, human. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for NKp44-positive group 3 innate lymphoid cell, human. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

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Target Cell for CSI:  NKp44-positive group 3 innate lymphoid cell, human (CL0001079)

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Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
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 High
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 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

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## Summary The **Overall** analysis of the [NKp44-positive group 3 innate lymphoid cell, human](/details-cell/CL0001079), identifies it as a highly metabolically active immune cell. Its identity is defined by a unique combination of genes essential for innate lymphoid cell (ILC) development, such as [IL7R](/details-gene/3575), and effector function, like [LTB](/details-gene/4050). The most prominent characteristic revealed by the data is an exceptionally strong gene signature related to aerobic respiration and energy production, suggesting these cells are primed for rapid and potent responses within their tissue microenvironments. ## Key Characteristics and Function The functional profile of [NKp44-positive group 3 innate lymphoid cell, human](/details-cell/CL0001079) is dominated by several key biological themes. While the associated p-values are high, the maximal effect sizes and high Cell Significance Index (CSI) scores for the top markers provide strong biological indications. * **High Metabolic Activity:** The most defining characteristic is an enrichment of genes involved in mitochondrial energy production. Top markers include multiple subunits of the cytochrome-c oxidase complex ([COX2](/details-gene/4513) and [COX1](/details-gene/4512)) and NADH dehydrogenase ([ND4L](/details-gene/4539)), as well as components of ATP synthase ([ATP8](/details-gene/4509), [ATP6](/details-gene/4508)). This, along with the high significance of [GAPDH](/details-gene/2597) from the glycolysis pathway, strongly suggests that these cells possess a high basal metabolic rate, likely to fuel their roles in surveillance and rapid cytokine production. * **Core ILC3 Identity and Signaling:** The cell's identity as a group 3 ILC is confirmed by the high significance of [IL7R](/details-gene/3575), a receptor critical for the development and survival of all ILCs ([Link](https://doi.org/10.1016/0092-8674(90)90342-c)). Furthermore, the presence of [LTB](/details-gene/4050) (Lymphotoxin Beta) as a top marker is particularly indicative of ILC3s, as this cytokine is crucial for the formation and maintenance of secondary lymphoid tissues. The expression of key signaling regulators like [NFKBIA](/details-gene/4792) and [DUSP1](/details-gene/1843) suggests that while poised for action, their inflammatory responses are under tight negative-feedback control. * **Active Transcriptional and Translational State:** A large number of top markers are involved in RNA and DNA binding, transcription, and protein synthesis, including [PCBP2](/details-gene/5094), [PABPC1](/details-gene/26986), [NPM1](/details-gene/4869), and [HNRNPA2B1](/details-gene/3181). This indicates a state of high transcriptional and translational activity, consistent with a cell type that must produce and secrete effector proteins as part of its primary function. * **Immune Surveillance and Interaction:** The high ranking of [B2M](/details-gene/567), a component of MHC class I molecules, implies that these cells are capable of interacting with other immune cells, such as cytotoxic [CD8-positive, alpha-beta T cells](/details-cell/CL0000625). The low CSI score for the T-cell receptor component [CD247](/details-gene/919) serves as a key anti-marker, distinguishing this innate cell from its adaptive T-cell counterparts. Similarly, the low significance of [CORO1A](/details-gene/11151), a gene associated with phagocytosis, reinforces its non-phagocytic, lymphoid lineage. ## Clinical Significance and Contextual Roles [NKp44-positive group 3 innate lymphoid cells](/details-cell/CL0001079) are primarily located at mucosal surfaces and play a critical role in maintaining barrier integrity, defending against extracellular pathogens, and orchestrating immune responses. The gene signature provides insights into their potential roles in health and disease. The high significance of [IL7R](/details-gene/3575) is clinically relevant, as mutations in this gene are known to cause T(-)B(+)NK(+) severe combined immunodeficiency (SCID), highlighting its indispensable role in lymphocyte development ([Link](https://doi.org/10.1038/3877)). The prominence of [LTB](/details-gene/4050) is also significant, as the lymphotoxin pathway is implicated in the pathogenesis of autoimmune diseases and the development of tertiary lymphoid structures in chronic inflammation and cancer. The strong metabolic profile, characterized by high expression of [COX1](/details-gene/4512) and [COX2](/details-gene/4513), suggests these cells are well-adapted to environments that may be hypoxic or metabolically demanding, such as inflamed tissues or the tumor microenvironment. This metabolic readiness may allow them to sustain effector functions under stress. Additionally, the high expression of the immediate-early gene [NFKBIA](/details-gene/4792), a key negative regulator of the NF-kappaB pathway, points to their role in balancing pro-inflammatory signals, a critical function at mucosal sites constantly exposed to microbial stimuli. Dysregulation of this balance could contribute to inflammatory bowel disease or other mucosal inflammatory conditions. ## Potential Mechanisms and Research Directions 1. **Hypothesis: NKp44+ ILC3s are defined by a state of 'metabolic pre-activation' that fuels rapid effector responses.** * **Surprising Findings:** The dominance of mitochondrial respiratory chain genes ([COX1](/details-gene/4512), [COX2](/details-gene/4513), [ND4L](/details-gene/4539)) as the most specific markers is unexpected. Typically, cell surface proteins or lineage-defining transcription factors are considered primary identifiers. This finding suggests that a specific, high-energy metabolic state is a more defining feature for these cells than many canonical markers. This state may be essential for their function as rapid first-responders at barrier surfaces. * **Testable Questions:** How does the single-cell metabolic flux profile (e.g., oxygen consumption rate) of resting NKp44+ ILC3s compare to that of naive T-cells or other ILC subsets? Does pharmacologic inhibition of the electron transport chain prevent the rapid, early-phase secretion of effector molecules like LTB and IL-22 following stimulation? 2. **Hypothesis: The constitutive co-expression of potent inflammatory effectors ([LTB](/details-gene/4050)) and key inflammatory inhibitors ([NFKBIA](/details-gene/4792), [DUSP1](/details-gene/1843)) establishes a tight rheostat that controls mucosal homeostasis.** * **Surprising Findings:** It is notable that genes encoding powerful negative regulators of inflammation rank so highly alongside pro-inflammatory cytokines. The high CSI for [NFKBIA](/details-gene/4792), an inhibitor that must be continuously synthesized due to its rapid degradation, suggests that a powerful, built-in braking system is a core, identifying feature of this cell. This implies their primary role might be less about initiating inflammation and more about precisely tuning its magnitude and duration. * **Testable Questions:** Upon stimulation with activating cytokines like IL-23, what is the temporal dynamic of [LTB](/details-gene/4050) versus [NFKBIA](/details-gene/4792) transcript and protein expression? Does silencing [NFKBIA](/details-gene/4792) in these cells lead to a hyper-inflammatory phenotype, characterized by exaggerated and prolonged cytokine production in response to a defined stimulus?