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Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease
Source paper: PMC12133578 | [
{
"end": 87,
"label": "Tissue",
"start": 72,
"text": "small intestine"
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] | Single_Cell |
The immune–epithelial–stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. | [] | Single_Cell |
To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. | [
{
"end": 88,
"label": "CellType",
"start": 82,
"text": "immune"
},
{
"end": 101,
"label": "CellType",
"start": 90,
"text": "parenchymal"
},
{
"end": 122,
"label": "CellType",
"start": 106,
"text": "epithelial cells"
}
] | Single_Cell |
Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. | [
{
"end": 47,
"label": "CellType",
"start": 25,
"text": "epithelial populations"
},
{
"end": 194,
"label": "CellType",
"start": 167,
"text": "enteroendocrine populations"
}
] | Single_Cell |
Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4 T cells, intraepithelial lymphocytes, CD8 and γδ T cell subsets, with skewed T cell antigen receptor repertoires. | [
{
"end": 15,
"label": "CellType",
"start": 0,
"text": "Mucosal T cells"
},
{
"end": 67,
"label": "CellType",
"start": 57,
"text": "regulatory"
},
{
"end": 106,
"label": "CellType",
"start": 72,
"text": "follicular helper-like CD4 T cells"
},
{
"end": 1... | Single_Cell |
Mucosal changes remained detectable despite treatment, representing a persistent immune–epithelial ‘scar’. | [] | Single_Cell |
Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell–B cell interactions. | [
{
"end": 155,
"label": "CellType",
"start": 124,
"text": "CD-specific lymphoid aggregates"
}
] | Single_Cell |
Receptor–ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment. | [] | Single_Cell |
Celiac disease (CD) is a common gastrointestinal disorder affecting 1–2% of European and North American populations, in which small intestinal inflammation and damage are driven by aberrant adaptive immune responses to gluten . | [] | Single_Cell |
The only treatment is a lifelong gluten-free diet (GFD). | [] | Single_Cell |
There is an unmet therapeutic need for those living with CD, including refractory CD, where ongoing tissue damage occurs despite a GFD . | [] | Single_Cell |
A strong genetic component drives CD, dominated by HLA-DQ2 and HLA-DQ8 (ref. ), | [] | Single_Cell |
with association studies identifying over 40 non-HLA genomic loci, implicating over 100 candidate genes and a role for immunoregulatory mechanisms . | [] | Single_Cell |
Murine models implicate viral infection as a trigger of loss of tolerance driving CD pathogenesis , a hypothesis supported by epidemiological studies . | [] | Single_Cell |
CD pathophysiology is multifactorial with several cell types implicated . | [] | Single_Cell |
Dietary gluten is deamidated by tissue transglutaminase 2, and deamidated gluten peptides presented via HLA-DQ2/HLA-DQ8 to CD4 T cells . | [
{
"end": 134,
"label": "CellType",
"start": 123,
"text": "CD4 T cells"
}
] | Single_Cell |
Gluten-specific CD4 T cells possess a distinct type 1 helper T (T H 1)/follicular helper T (T FH ) cell phenotype, emphasizing the importance of T cell–B cell interactions . | [
{
"end": 27,
"label": "CellType",
"start": 16,
"text": "CD4 T cells"
}
] | Single_Cell |
Tissue plasma and B cells may present gluten peptides via HLA-DQ . | [
{
"end": 13,
"label": "CellType",
"start": 0,
"text": "Tissue plasma"
},
{
"end": 25,
"label": "CellType",
"start": 18,
"text": "B cells"
}
] | Single_Cell |
Subsequent stimulation of disease-specific plasma cells drives anti-tissue transglutaminase and anti-deamidated gliadin peptide antibody production. | [] | Single_Cell |
Gluten-specific T cells are necessary but not sufficient to generate mucosal damage . | [
{
"end": 23,
"label": "CellType",
"start": 16,
"text": "T cells"
}
] | Single_Cell |
The mechanisms by which this response leads to tissue architectural change are incompletely understood. | [] | Single_Cell |
Intraepithelial lymphocytes (IELs), mainly CD8 T IELs, are highly enriched in CD, likely driven by epithelial and myeloid-derived interleukin (IL)-15, in combination with CD4 T cell-derived IL-2, IL-21 and interferon gamma (IFNγ) . | [
{
"end": 34,
"label": "CellType",
"start": 0,
"text": "Intraepithelial lymphocytes (IELs)"
},
{
"end": 53,
"label": "CellType",
"start": 43,
"text": "CD8 T IELs"
}
] | Single_Cell |
IELs may be directly involved in EC killing in a T cell antigen receptor (TCR)-independent manner, via NKG2C and NKG2D and their epithelial ligands MICA and HLA-E . | [] | Single_Cell |
However, the transcriptional state and involvement of TCR signaling in these CD8 T cell populations remains unclear. | [
{
"end": 99,
"label": "CellType",
"start": 77,
"text": "CD8 T cell populations"
}
] | Single_Cell |
While novel treatments are under development , recent therapeutic trials targeting gluten degradation, gluten-specific CD4 T cell tolerance and IL-15 have been unsuccessful . | [] | Single_Cell |
However, therapies including tissue transglutaminase inhibitors and inducers of immune tolerance have shown promise . | [] | Single_Cell |
Single-cell transcriptomics have redefined cellular landscapes in the gastrointestinal tract , offering insights into CD immunopathology . | [
{
"end": 92,
"label": "Tissue",
"start": 70,
"text": "gastrointestinal tract"
}
] | Single_Cell |
Recent studies have sought to understand the cellular basis of CD using mass cytometry, including studies of refractory CD , gluten-specific T cells , and mucosal and circulating T cells . | [
{
"end": 148,
"label": "CellType",
"start": 141,
"text": "T cells"
},
{
"end": 162,
"label": "CellType",
"start": 155,
"text": "mucosal"
},
{
"end": 186,
"label": "CellType",
"start": 179,
"text": "T cells"
}
] | Single_Cell |
Single-cell RNA sequencing (scRNA-seq) has been used to study mucosal immune cells , T cells , circulating immune cells and mucosal plasma cells . | [
{
"end": 82,
"label": "CellType",
"start": 62,
"text": "mucosal immune cells"
},
{
"end": 92,
"label": "CellType",
"start": 85,
"text": "T cells"
},
{
"end": 119,
"label": "CellType",
"start": 107,
"text": "immune cells"
},
{
"end": 144,
"label": "... | Single_Cell |
Here, we combined single-cell and spatial transcriptomics to define the network of intestinal immune, epithelial and parenchymal cell populations in adults and children with CD. | [
{
"end": 112,
"label": "CellType",
"start": 102,
"text": "epithelial"
},
{
"end": 145,
"label": "CellType",
"start": 117,
"text": "parenchymal cell populations"
}
] | Single_Cell |
Our description of spatially localized immune–parenchymal interactions driving inflammation and remodeling of the mucosa, and with specific disease-associated T cell subsets occupying distinct mucosal niches, will facilitate identification of therapeutic targets. | [
{
"end": 120,
"label": "Tissue",
"start": 114,
"text": "mucosa"
},
{
"end": 173,
"label": "CellType",
"start": 159,
"text": "T cell subsets"
},
{
"end": 207,
"label": "Tissue",
"start": 193,
"text": "mucosal niches"
}
] | Single_Cell |
We generated scRNA-seq profiles of duodenal epithelial, immune and parenchymal populations from 35 participants: 21 with CD (16 children, 5 adults) and 14 controls (5 children, 9 adults; Fig. 1 and Supplementary Table 1 ). | [
{
"end": 54,
"label": "CellType",
"start": 35,
"text": "duodenal epithelial"
},
{
"end": 62,
"label": "CellType",
"start": 56,
"text": "immune"
},
{
"end": 90,
"label": "CellType",
"start": 67,
"text": "parenchymal populations"
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] | Single_Cell |
We used complementary single-cell techniques for adult and pediatric datasets, with 86,442 cells sequenced. | [] | Single_Cell |
In adults (datasets 1 and 3), we performed scRNA-seq (10x Genomics) on epithelial, immune (Supplementary Fig. 1a,b ), stromal and endothelial cells. | [
{
"end": 81,
"label": "CellType",
"start": 71,
"text": "epithelial"
},
{
"end": 89,
"label": "CellType",
"start": 83,
"text": "immune"
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{
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"label": "CellType",
"start": 118,
"text": "stromal"
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{
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"label": "CellType",
"... | Single_Cell |
In children (dataset 2), we performed targeted scRNA-seq (BD Rhapsody; 504 targeted gene primer pairs) and surface protein expression (79 oligonucleotide-conjugated antibodies) on intestinal immune cells (Supplementary Fig. 1c,d and Supplementary Tables 2 and 3 ). | [
{
"end": 203,
"label": "CellType",
"start": 180,
"text": "intestinal immune cells"
}
] | Single_Cell |
We analyzed EPCAM epithelial populations from dataset 1. | [
{
"end": 40,
"label": "CellType",
"start": 12,
"text": "EPCAM epithelial populations"
}
] | Single_Cell |
Nine transcriptionally distinct epithelial cell (EC) clusters were identified, representing progenitor, secretory and absorptive lineages along the developmental progression of the crypt–villus axis (Fig. 2a,b , Extended Data Fig. 1a and Supplementary Table 4 ). | [
{
"end": 61,
"label": "CellType",
"start": 32,
"text": "epithelial cell (EC) clusters"
},
{
"end": 102,
"label": "CellType",
"start": 92,
"text": "progenitor"
},
{
"end": 113,
"label": "CellType",
"start": 104,
"text": "secretory"
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{
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... | Single_Cell |
BEST4 enterocytes ( BEST4 CA7 CPA2 ), first identified in the colon , were seen, expressing CFTR and showing chloride channel activity (Fig. 2b and Extended Data Fig. 1a ). | [
{
"end": 17,
"label": "CellType",
"start": 0,
"text": "BEST4 enterocytes"
},
{
"end": 67,
"label": "Tissue",
"start": 62,
"text": "colon"
}
] | Single_Cell |
Goblet cells ( ITLN1 MUC2 SPINK4 ) and tuft cells ( PLCG2 TRPM5 IRAG2 ) were also identified. | [
{
"end": 12,
"label": "CellType",
"start": 0,
"text": "Goblet cells"
},
{
"end": 49,
"label": "CellType",
"start": 39,
"text": "tuft cells"
}
] | Single_Cell |
A LYZ Paneth cell-like population ( MMP7 REG1A SOD3 PLA2G2A ) was also identified (Fig. 2a,b ), although defensin gene expression was not detected. | [
{
"end": 33,
"label": "CellType",
"start": 2,
"text": "LYZ Paneth cell-like population"
}
] | Single_Cell |
This population expressed PGC , mucins including MUC5AC , MUC1 and MUC6 and AQP5 , suggesting it also contained Brunner’s gland cells or ectopic gastric pyloric gland cells. | [
{
"end": 133,
"label": "CellType",
"start": 112,
"text": "Brunner’s gland cells"
},
{
"end": 172,
"label": "CellType",
"start": 137,
"text": "ectopic gastric pyloric gland cells"
}
] | Single_Cell |
This cell type was enriched in active celiac disease (ACD; Fig. 2c,d ), perhaps in response to IFNγ. | [] | Single_Cell |
Thus, this population could represent inflammation-driven gastric cell metaplasia . | [] | Single_Cell |
Transit-amplifying (TA) cells were increased in CD, along with enrichment of uniform manifold approximation and projection (UMAP) areas corresponding to EC progenitors (stem cells, TA cells and early enterocytes; Fig. 2c,d ). | [
{
"end": 29,
"label": "CellType",
"start": 0,
"text": "Transit-amplifying (TA) cells"
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{
"end": 167,
"label": "CellType",
"start": 153,
"text": "EC progenitors"
},
{
"end": 179,
"label": "CellType",
"start": 169,
"text": "stem cells"
},
{
"end": 189,... | Single_Cell |
This persisted in treated celiac disease (TCD; Extended Data Fig. 1b,c ). | [] | Single_Cell |
In parallel, more actively cycling ECs were observed in ACD and TCD (Extended Data Fig. 1d,e ). | [
{
"end": 38,
"label": "CellType",
"start": 35,
"text": "ECs"
}
] | Single_Cell |
Pseudotime analyses identified epithelial developmental trajectories, from undifferentiated progenitor states toward absorptive and secretory lineages (Fig. 2e ). | [] | Single_Cell |
In CD, ECs were shifted to earlier pseudotime states, with loss of mature ECs (Fig. 2f ). | [
{
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"label": "CellType",
"start": 7,
"text": "ECs"
},
{
"end": 77,
"label": "CellType",
"start": 74,
"text": "ECs"
}
] | Single_Cell |
CCL25 , encoding the ligand for CCR9 (implicated in CD pathogenesis ), was expressed predominantly by progenitor cells (Fig. 2b and Extended Data Fig. 1f ). | [
{
"end": 118,
"label": "CellType",
"start": 102,
"text": "progenitor cells"
}
] | Single_Cell |
We examined putative EC functions through functional gene-set analysis (Extended Data Fig. 1a ), identifying functions of secretory Paneth-like/Brunner’s gland cells (secreted protein and vesicle pathways), BEST4 enterocytes (chloride/anion channel activity), tuft cells (taste perception) and enteroendocrine cells (EEC... | [
{
"end": 165,
"label": "CellType",
"start": 122,
"text": "secretory Paneth-like/Brunner’s gland cells"
},
{
"end": 224,
"label": "CellType",
"start": 207,
"text": "BEST4 enterocytes"
},
{
"end": 270,
"label": "CellType",
"start": 260,
"text": "tuft cells"
},... | Single_Cell |
Mature enterocytes expressed key metabolic and macronutrient catabolic pathways, and active transport and absorption mechanisms. | [
{
"end": 18,
"label": "CellType",
"start": 7,
"text": "enterocytes"
}
] | Single_Cell |
Early ECs and TA cells did not express these pathways. | [
{
"end": 9,
"label": "CellType",
"start": 6,
"text": "ECs"
},
{
"end": 22,
"label": "CellType",
"start": 14,
"text": "TA cells"
}
] | Single_Cell |
Absorptive function genes were limited to cell states at the end of absorptive epithelium pseudotime trajectories, consistent with EC development along the crypt–villus axis (Fig. 2g ). | [
{
"end": 173,
"label": "Tissue",
"start": 156,
"text": "crypt–villus axis"
}
] | Single_Cell |
Notably, gene sets related to lipid, carbohydrate, cholesterol, vitamin and iron processing and absorption were all downregulated in mature enterocytes in ACD (Extended Data Fig. 1g–i ). | [
{
"end": 151,
"label": "CellType",
"start": 140,
"text": "enterocytes"
}
] | Single_Cell |
These transcriptional changes normalized in TCD, although some pathways, including fructose metabolism and lipid catabolism, remained reduced (Extended Data Fig. 1h ). | [] | Single_Cell |
Overall, absorptive capacity is reduced in ACD not simply by reduction in villus surface area, but through a relative increase of EC progenitors lacking absorptive machinery, and pathway downregulation in mature enterocytes. | [
{
"end": 144,
"label": "CellType",
"start": 130,
"text": "EC progenitors"
},
{
"end": 223,
"label": "CellType",
"start": 212,
"text": "enterocytes"
}
] | Single_Cell |
ECs in ACD upregulated multiple antigen-presentation molecules, including classical HLA class I and class II genes (except HLA-DQ ) and nonclassical genes including HLA-E and HLA-F (Fig. 2h ). | [
{
"end": 3,
"label": "CellType",
"start": 0,
"text": "ECs"
}
] | Single_Cell |
Interferon-stimulated genes (types I and II) dominated the epithelial response, including STAT1 (Fig. 2h and Supplementary Table 5 ). | [] | Single_Cell |
The major disease-associated responses were observed in all EC lineages (Extended Data Fig. 1j–l ), including antigen-presentation pathways, type I/II interferon responses, lymphocyte-mediated immunity and cytotoxicity and cell adhesion regulation (Extended Data Fig. 1m,n ). | [
{
"end": 71,
"label": "CellType",
"start": 60,
"text": "EC lineages"
}
] | Single_Cell |
Some transcriptional changes were cell-type specific. | [] | Single_Cell |
IL32 was highly expressed in ACD by mature enterocytes (Extended Data Fig. 1k ), perhaps regulated by interferons. | [
{
"end": 54,
"label": "CellType",
"start": 43,
"text": "enterocytes"
}
] | Single_Cell |
The reduction of fatty acid catabolism/transport ( APOA1 , FABP2 ), metal ion transport (iron: FTH1 , FTL ; zinc: SLC39A4 ) and carbohydrate metabolism ( ALDOB , PCK1 ) was restricted to absorptive lineages, mainly mature enterocytes (Extended Data Fig. 1k,n ). | [
{
"end": 206,
"label": "CellType",
"start": 187,
"text": "absorptive lineages"
},
{
"end": 233,
"label": "CellType",
"start": 222,
"text": "enterocytes"
}
] | Single_Cell |
Progenitor cells upregulated genes associated with cell division and differentiation, and downregulated those associated with tissue repair and homeostasis (Extended Data Fig. 1m,n ). | [
{
"end": 16,
"label": "CellType",
"start": 0,
"text": "Progenitor cells"
}
] | Single_Cell |
Secretory lineages showed increased expression of gut hormone genes, LYZ , and chemokines ( CXCL17 , CXCL2 ; Extended Data Fig. 1l ). | [
{
"end": 18,
"label": "CellType",
"start": 0,
"text": "Secretory lineages"
}
] | Single_Cell |
The duodenum, where CD inflammation predominates, has sensory and neurohormonal functions. | [
{
"end": 12,
"label": "Tissue",
"start": 4,
"text": "duodenum"
}
] | Single_Cell |
We extended EEC clustering, revealing multiple transcriptional states, including NEUROG3 progenitors and EEC subtypes, which showed similar CD-related transcriptional changes to other ECs (Extended Data Fig. 2 ). | [
{
"end": 100,
"label": "CellType",
"start": 81,
"text": "NEUROG3 progenitors"
},
{
"end": 117,
"label": "CellType",
"start": 105,
"text": "EEC subtypes"
},
{
"end": 187,
"label": "CellType",
"start": 184,
"text": "ECs"
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] | Single_Cell |
EEC proportions altered in CD, with increases in NEUROG3 progenitor cells and somatostatin-producing D cells (Extended Data Fig. 2i–k ). | [
{
"end": 73,
"label": "CellType",
"start": 49,
"text": "NEUROG3 progenitor cells"
},
{
"end": 108,
"label": "CellType",
"start": 78,
"text": "somatostatin-producing D cells"
}
] | Single_Cell |
In adults (dataset 1), CD4 T cells formed subsets dominated by T H 1-polarized and IL-17-producing helper T (T H 17)-polarized effectors, as well as small naive and FOXP3 regulatory populations (Fig. 3a–c and Supplementary Table 6 ). | [
{
"end": 34,
"label": "CellType",
"start": 23,
"text": "CD4 T cells"
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{
"end": 78,
"label": "CellType",
"start": 63,
"text": "T H 1-polarized"
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{
"end": 136,
"label": "CellType",
"start": 83,
"text": "IL-17-producing helper T (T H 17)-polarized effectors"
... | Single_Cell |
There was a cluster of T FH -like CD4 T cells expressing PDCD1 , BTLA , CD28 , ICOS and intermediate CXCR5 . | [
{
"end": 46,
"label": "CellType",
"start": 23,
"text": "T FH -like CD4 T cells "
}
] | Single_Cell |
Dataset 2 (pediatric) contained analogous subsets (Extended Data Fig. 3a ), including CD31 CR2 recent thymic emigrants , a CCR7 T FH -like subset and the T FH -like subset expressing PD1, ICOS, CTLA4, BTLA and CD161 at the protein level (Fig. 3d,e ). | [
{
"end": 118,
"label": "CellType",
"start": 86,
"text": "CD31 CR2 recent thymic emigrants"
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{
"end": 145,
"label": "CellType",
"start": 123,
"text": "CCR7 T FH -like subset"
},
{
"end": 171,
"label": "CellType",
"start": 154,
"text": "T FH -like subset"
}
... | Single_Cell |
This T FH -like population in adults and children showed similar phenotypic profiles to those of gut-resident gluten-specific CD4 T cells in CD (Extended Data Fig. 3b ), and expressed TOX2 , CD200 , IL21 and CXCL13 . | [
{
"end": 26,
"label": "CellType",
"start": 5,
"text": "T FH -like population"
},
{
"end": 137,
"label": "CellType",
"start": 126,
"text": "CD4 T cells"
}
] | Single_Cell |
The cluster showed enrichment of TRBV7-2 , a V-gene enriched in gluten-specific CD4 T cell HLA-DQ2.5 TCR repertoires . | [] | Single_Cell |
T reg and T FH -like CD4 T cells were increased in ACD in adults and children (Fig. 3f–i ). | [
{
"end": 5,
"label": "CellType",
"start": 0,
"text": "T reg"
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{
"end": 32,
"label": "CellType",
"start": 10,
"text": "T FH -like CD4 T cells"
}
] | Single_Cell |
T cell populations showed distinct cytokine and chemokine expression patterns (Extended Data Fig. 3c ). | [
{
"end": 18,
"label": "CellType",
"start": 0,
"text": "T cell populations"
}
] | Single_Cell |
The CD-associated T FH -like population, showed high CXCL13 and IL21 expression, with IFNG and IL21 coexpression (Fig. 3j,k ), similarly to gluten-specific T cells . | [
{
"end": 39,
"label": "CellType",
"start": 18,
"text": "T FH -like population"
},
{
"end": 163,
"label": "CellType",
"start": 156,
"text": "T cells"
}
] | Single_Cell |
T FH -like cells expressed TNFSF8 , CCL1 , CCL22 and CXCL10 , as well as IL17F (Extended Data Fig. 3c ). | [
{
"end": 16,
"label": "CellType",
"start": 0,
"text": "T FH -like cells"
}
] | Single_Cell |
IL17F expression was not seen in the IL17A RORC IL23R CCR6 T H 17 population, nor did the T H 17 cluster show TRBV7-2 enrichment (Extended Data Fig. 3b,d ). | [
{
"end": 76,
"label": "CellType",
"start": 37,
"text": "IL17A RORC IL23R CCR6 T H 17 population"
},
{
"end": 104,
"label": "CellType",
"start": 90,
"text": "T H 17 cluster"
}
] | Single_Cell |
Oral gluten challenge in CD drives rapid circulating cytokine responses, including IL-2, CXCL8, CXCL10 and IL-6 (ref. ). | [] | Single_Cell |
CXCL8 expression was highest in CCR7 T FH CD4 T cells, CXCL10 was detected in T FH -like CD4 T cells, while IL6 was detected in T reg cells (Extended Data Fig. 3c ). | [
{
"end": 53,
"label": "CellType",
"start": 32,
"text": "CCR7 T FH CD4 T cells"
},
{
"end": 100,
"label": "CellType",
"start": 78,
"text": "T FH -like CD4 T cells"
},
{
"end": 139,
"label": "CellType",
"start": 128,
"text": "T reg cells"
}
] | Single_Cell |
IL2 expression was low within the CD4 compartment, as expected without gluten challenge. | [] | Single_Cell |
We examined transcription factor (TF), and regulon expression within CD4 subsets, with canonical TFs and regulons of T H 17 and T reg cell function expressed as expected (Extended Data Fig. 3e–g ). | [
{
"end": 80,
"label": "CellType",
"start": 69,
"text": "CD4 subsets"
}
] | Single_Cell |
IKZF1 and its regulon were upregulated in T FH -like cells, with intermediate expression of RUNX1 , BATF and IRF3 . | [
{
"end": 58,
"label": "CellType",
"start": 42,
"text": "T FH -like cells"
}
] | Single_Cell |
We examined B cell lineages in dataset 2 (pediatric; Extended Data Fig. 4a,b ). | [
{
"end": 27,
"label": "CellType",
"start": 12,
"text": "B cell lineages"
}
] | Single_Cell |
Both IgA and IgM plasma cells were increased in CD (Extended Data Fig. 4c–f ). | [
{
"end": 8,
"label": "CellType",
"start": 5,
"text": "IgA"
},
{
"end": 29,
"label": "CellType",
"start": 13,
"text": "IgM plasma cells"
}
] | Single_Cell |
A population of CXCR5 B cells ( MS4A1 CD19 CD20 ) were present, with a shift toward the CD27 memory B cell phenotype in CD. | [
{
"end": 29,
"label": "CellType",
"start": 16,
"text": "CXCR5 B cells"
}
] | Single_Cell |
Gene signatures of age-related B cells (an inflammation-associated population in autoimmune disease ), including ITGAM , ITGAX , CD86 and BATF , were expressed most highly in CD27 B cell populations, while a key age-related B cell TF, TBX21 , was highly expressed in cycling B cells (Extended Data Fig. 4b ). | [
{
"end": 38,
"label": "CellType",
"start": 31,
"text": "B cells"
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{
"end": 198,
"label": "CellType",
"start": 175,
"text": "CD27 B cell populations"
},
{
"end": 282,
"label": "CellType",
"start": 275,
"text": "B cells"
}
] | Single_Cell |
HLA class II gene and protein expression, specifically HLA-DQ , was highest in CD27 and cycling B cells (Extended Data Fig. 4g,h ). | [
{
"end": 83,
"label": "CellType",
"start": 79,
"text": "CD27"
},
{
"end": 103,
"label": "CellType",
"start": 96,
"text": "B cells"
}
] | Single_Cell |
Intestinal myeloid cell populations are impacted by CD and may be involved in antigen presentation and oral tolerance . | [
{
"end": 35,
"label": "CellType",
"start": 0,
"text": "Intestinal myeloid cell populations"
}
] | Single_Cell |
Myeloid cells (dataset 2) formed 11 transcriptionally distinct clusters, including macrophages, conventional dendritic cells and plasmacytoid dendritic cells (Supplementary Fig. 2a–c ). | [
{
"end": 13,
"label": "CellType",
"start": 0,
"text": "Myeloid cells"
},
{
"end": 94,
"label": "CellType",
"start": 83,
"text": "macrophages"
},
{
"end": 124,
"label": "CellType",
"start": 96,
"text": "conventional dendritic cells"
},
{
"end": 157,
... | Single_Cell |
HLA-DQ expression was highest on macrophage populations, particularly CD163 cells. | [
{
"end": 55,
"label": "CellType",
"start": 33,
"text": "macrophage populations"
},
{
"end": 81,
"label": "CellType",
"start": 70,
"text": "CD163 cells"
}
] | Single_Cell |
In contrast to prior studies , CD163 macrophages were reduced in ACD, with expansion of a conventional dendritic cell 2 population, which showed increased IL-1B expression (Supplementary Fig. 2d,e ). | [
{
"end": 48,
"label": "CellType",
"start": 31,
"text": "CD163 macrophages"
},
{
"end": 130,
"label": "CellType",
"start": 90,
"text": "conventional dendritic cell 2 population"
}
] | Single_Cell |
Intestinal CD8 T cells showed considerable heterogeneity in transcriptional states, with multiple tissue-resident memory CD8 T (T RM ) cells, including an ITGAE IL7R population, a CCL4 CD69 ITGAE population and two subsets of ITGAE T RM cells (Fig. 4 , Extended Data Fig. 5a and Supplementary Table 7 ). | [
{
"end": 22,
"label": "CellType",
"start": 0,
"text": "Intestinal CD8 T cells"
},
{
"end": 140,
"label": "CellType",
"start": 98,
"text": "tissue-resident memory CD8 T (T RM ) cells"
},
{
"end": 176,
"label": "CellType",
"start": 155,
"text": "ITGAE IL7R popul... | Single_Cell |
These aligned with gene signatures defining subsets of bona fide human T RM cells . | [] | Single_Cell |
FGFBP2 effectors aligned with previously described ITGB2 ITGAE T RM cells, while T RM (1), T RM (2) and cycling subsets aligned with CD103 T RM cells (Extended Data Fig. 5b ). | [
{
"end": 73,
"label": "CellType",
"start": 51,
"text": "ITGB2 ITGAE T RM cells"
},
{
"end": 89,
"label": "CellType",
"start": 81,
"text": "T RM (1)"
},
{
"end": 99,
"label": "CellType",
"start": 91,
"text": "T RM (2)"
},
{
"end": 119,
"label": "Cel... | Single_Cell |
CCL4 and IL7R populations likely represent intermediate states in T RM cell development. | [
{
"end": 4,
"label": "CellType",
"start": 0,
"text": "CCL4"
},
{
"end": 25,
"label": "CellType",
"start": 9,
"text": "IL7R populations"
}
] | Single_Cell |
Small natural IEL and cycling MKI67 populations were seen (Extended Data Fig. 5b,c ). | [
{
"end": 17,
"label": "CellType",
"start": 6,
"text": "natural IEL"
},
{
"end": 47,
"label": "CellType",
"start": 30,
"text": "MKI67 populations"
}
] | Single_Cell |
Analogous CD8 T cell subsets were seen in dataset 2 (Fig. 4d,e and Extended Data Fig. 5a ), with additional resolution for tissue-resident γδ T cells, and innate-like T cells (mucosal-associated invariant T cells and Vδ2Vγ9 cells). | [
{
"end": 28,
"label": "CellType",
"start": 10,
"text": "CD8 T cell subsets"
},
{
"end": 149,
"label": "CellType",
"start": 123,
"text": "tissue-resident γδ T cells"
},
{
"end": 174,
"label": "CellType",
"start": 167,
"text": "T cells"
},
{
"end": 212,
... | Single_Cell |
We analyzed subsets relevant to CD, including natural killer (NK)-receptor expressing IELs and killer-cell immunoglobulin-like receptor (KIR)-positive CD8 T cells . | [
{
"end": 90,
"label": "CellType",
"start": 46,
"text": "natural killer (NK)-receptor expressing IELs"
},
{
"end": 162,
"label": "CellType",
"start": 151,
"text": "CD8 T cells"
}
] | Single_Cell |
KLRC1 (NKG2A) was expressed by CCL4 cells, while KLRC2 (NKG2C) was expressed by resident IL7R , T RM (1) and T RM (2) subsets (Extended Data Fig. 5c,d ). | [
{
"end": 41,
"label": "CellType",
"start": 31,
"text": "CCL4 cells"
},
{
"end": 93,
"label": "CellType",
"start": 80,
"text": "resident IL7R"
},
{
"end": 105,
"label": "CellType",
"start": 96,
"text": "T RM (1) "
},
{
"end": 125,
"label": "CellType... | Single_Cell |
Inhibitory KIR molecule expression was confined to a small FGFBP2 effector population. | [
{
"end": 85,
"label": "CellType",
"start": 59,
"text": "FGFBP2 effector population"
}
] | Single_Cell |
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