CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection

Cortez, Victor S.; Cervantes-Barragán, Luisa; Song, Christina; Gilfillan, Susan; McDonald, Keely G.; Tussiwand, Roxane; Edelson, Brian T.; Murakami, Yoshinori; Murphy, Kenneth M.; Newberry, Rodney D.; Sibley, L. David; Colonna, Marco

doi:10.1084/jem.20130904

Cited by 50 publications

(44 citation statements)

References 41 publications

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“…Expanded clones followed pseudotime trajectory analysis and displayed intra-clonal plasticity: less expanded clones spread among heterogenous subsets, while highly expanded clones were found in the homogenous cluster of CD4-IELs. A possible explanation for this finding is that the less expanded clones lacked additional signals, such as TCR ligands or environmental components, required for full differentiation into CD4-IELs (Cervantes- Barragan et al, 2017;Cortez et al, 2014;Mucida et al, 2013;Reis et al, 2014;. The clonal analyses presented here, including the TCR sharing of CD4-IELs derived from Treg or from Tconv, corroborate previous studies suggesting a lineage relationship between Tregs and IELs (Bilate et al, 2016;Sujino et al, 2016).…”

Section: Discussionsupporting

confidence: 86%

T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

Bilate

London

Castro

et al. 2020

Preprint

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The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneous T cell population with cytotoxic and regulatory properties. Migrating peripheral CD4 + T cells, including regulatory (Treg) and conventional T cells (Tconv), acquire an IEL (CD4-IEL) program upon arrival at the epithelium. However, the specific role of the T cell receptor (TCR) in this process remains unclear. Single-cell TCR repertoire and transcriptomic analysis of intraepithelial CD4 + T cells revealed different extents of clonal expansion and TCR overlap between cell states; fully differentiated CD4-IELs from Tregs or Tconvs were the least diverse. Conditional deletion of TCR on differentiating CD4 + T cells or of MHCII on intestinal epithelial cells prevented CD4-IEL differentiation.However, TCR ablation on developed CD4-IELs did not affect their accumulation.These results indicate that local recognition of a limited set of antigens is an essential signal for the differentiation and adaptation of T cells to the epithelium.

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Section: Discussionsupporting

confidence: 86%

T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

Bilate

London

Castro

et al. 2020

Preprint

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“…Mouse knockout showed Fgl2 is required for Treg function and prevention of spontaneous autoimmunity (Shalev et al, 2008). Similarly, CRTAM encodes a T cell adhesion molecule that is recently recognized to critically control the differentiation of CD4+ cells into inflammatory Th17 cells (Cortez et al, 2014). Thus, gender-specific regulation of FGL2 and CRTAM , which to our knowledge has not been reported, may contribute in part to gender-linked differences for autoimmune disease.…”

Section: Resultsmentioning

confidence: 99%

Individuality and Variation of Personal Regulomes in Primary Human T Cells

et al. 2015

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Here we survey variation and dynamics of active regulatory elements genome-wide using longitudinal samples from human individuals. We applied Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) to map chromatin accessibility in primary CD4+ T cells isolated from standard blood draws of 12 healthy volunteers over time, from cancer patients, and during T cell activation. Over 4,000 predicted regulatory elements (7.2%) showed reproducible variation in accessibility between individuals. Gender was the most significant attributable source of variation. ATAC-seq revealed previously undescribed elements that escape X chromosome inactivation and predicted gender-specific gene regulatory networks across autosomes, which coordinately affect genes with immune function. Noisy regulatory elements with personal variation in accessibility are significantly enriched for autoimmune disease loci. Over one third of regulome variation lacked genetic variation in cis, suggesting contributions from environmental or epigenetic factors. These results refine concepts of human individuality and provide a foundational reference for comparing disease-associated regulomes.

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“…In addition to overall differences between transcriptomes, 2-by-2-fold comparisons of all cell populations identified a limited cohort of genes for blood versus tonsil subsets, likely reflecting their distinct microenvironments ( Figure 1H). Notably, Ts-NK and ieILC1 expressed CRTAM, encoding an adhesion molecule that facilitates tissue retention (Cortez et al, 2014). Blood NKs expressed the gene for TGFBR3, which modulates transforming growth factor b (TGF-b) signaling and is distinctive from the classical TGFBR2 receptor that mediates TGF-b imprinting in ILC1s .…”

Section: Transcriptional Programs Of Human Nk and Ieilc1s From Distinmentioning

confidence: 99%

Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells

Collins

Cella

Porter

et al. 2019

Cell

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131

116

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CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection

Abstract: Interactions between cell adhesion molecules CRTAM and Cadm1 regulate the residency and maintenance of CD4+CD8+ and CD4+ T cells in the gut that can influence the immune response to infection.

Cited by 50 publications

References 41 publications

T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

T cell receptor is required for differentiation but not maintenance of intestinal intraepithelial lymphocytes

Individuality and Variation of Personal Regulomes in Primary Human T Cells

Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells

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