Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program.
Animals
Cell Differentiation
Cell Lineage
Cells, Cultured
Chromatin Assembly and Disassembly
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genomic Imprinting
Intestinal Mucosa
/ immunology
Intraepithelial Lymphocytes
/ immunology
Lymph Nodes
/ immunology
Mice, Knockout
Phenotype
RNA-Seq
Single-Cell Analysis
T-Lymphocytes, Regulatory
/ immunology
Transcription Factors
/ genetics
Transcription, Genetic
Transcriptome
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
21
02
2020
accepted:
19
01
2021
pubmed:
10
3
2021
medline:
29
6
2021
entrez:
9
3
2021
Statut:
ppublish
Résumé
Mesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria and epithelium, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we uncovered the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (T
Identifiants
pubmed: 33686285
doi: 10.1038/s41590-021-00883-8
pii: 10.1038/s41590-021-00883-8
pmc: PMC8251700
mid: NIHMS1710860
doi:
Substances chimiques
Th-POK protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
449-459Subventions
Organisme : NIAID NIH HHS
ID : R01 AI157137
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK093674
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113375
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144827
Pays : United States
Références
Mucida, D. et al. Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115, 1923–1933 (2005).
pubmed: 15937545
pmcid: 1142115
doi: 10.1172/JCI24487
Bilate, A. M. & Lafaille, J. J. Induced CD4
pubmed: 22224762
doi: 10.1146/annurev-immunol-020711-075043
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
pubmed: 24226770
doi: 10.1038/nature12721
Hadis, U. et al. Intestinal tolerance requires gut homing and expansion of FoxP3
pubmed: 21333554
doi: 10.1016/j.immuni.2011.01.016
Sujino, T. et al. Tissue adaptation of regulatory and intraepithelial CD4
pubmed: 27256884
pmcid: 4968079
doi: 10.1126/science.aaf3892
Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).
pubmed: 21205640
doi: 10.1126/science.1198469
Atarashi, K. et al. T
pubmed: 23842501
doi: 10.1038/nature12331
Olivares-Villagómez, D. & Van Kaer, L. Intestinal intraepithelial lymphocytes: sentinels of the mucosal barrier. Trends Immunol. 39, 264–275 (2018).
pubmed: 29221933
doi: 10.1016/j.it.2017.11.003
McDonald, B. D., Jabri, B. & Bendelac, A. Diverse developmental pathways of intestinal intraepithelial lymphocytes. Nat. Rev. Immunol. 18, 514–525 (2018).
pubmed: 29717233
pmcid: 6063796
doi: 10.1038/s41577-018-0013-7
Vantourout, P. & Hayday, A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat. Rev. Immunol. 13, 88–100 (2013).
pubmed: 23348415
pmcid: 3951794
doi: 10.1038/nri3384
Reis, B. S., Rogoz, A., Costa-Pinto, F. A., Taniuchi, I. & Mucida, D. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4
pubmed: 23334789
pmcid: 3804366
doi: 10.1038/ni.2518
Reis, B. S., Hoytema van Konijnenburg, D. P., Grivennikov, S. I. & Mucida, D. Transcription factor T-bet regulates intraepithelial lymphocyte functional maturation. Immunity 41, 244–256 (2014).
pubmed: 25148025
pmcid: 4287410
doi: 10.1016/j.immuni.2014.06.017
Konkel, J. E. et al. Control of the development of CD8αα
pubmed: 21297643
pmcid: 3062738
doi: 10.1038/ni.1997
Bilate, A. M. et al. Tissue-specific emergence of regulatory and intraepithelial T cells from a clonal T cell precursor. Sci. Immunol. 1, eaaf7471 (2016).
pubmed: 28783695
pmcid: 6296461
doi: 10.1126/sciimmunol.aaf7471
Mucida, D. et al. Transcriptional reprogramming of mature CD4
pubmed: 23334788
pmcid: 3581083
doi: 10.1038/ni.2523
Rubtsov, Y. P. et al. Stability of the regulatory T cell lineage in vivo. Science 329, 1667–1671 (2010).
pubmed: 20929851
pmcid: 4262151
doi: 10.1126/science.1191996
Setoguchi, R. et al. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science 319, 822–825 (2008).
pubmed: 18258917
doi: 10.1126/science.1151844
Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2019).
doi: 10.1038/nbt.4314
Zemmour, D. et al. Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nat. Immunol. 19, 291–301 (2018).
pubmed: 29434354
pmcid: 6069633
doi: 10.1038/s41590-018-0051-0
Miragaia, R. J. et al. Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation. Immunity 50, 493–504.e7 (2019).
pubmed: 30737144
pmcid: 6382439
doi: 10.1016/j.immuni.2019.01.001
Bilate, A. M. et al. T cell receptor is required for differentiation, but not maintenance, of intestinal CD4
pubmed: 33022229
pmcid: 7677182
doi: 10.1016/j.immuni.2020.09.003
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
pubmed: 24097267
pmcid: 3959825
doi: 10.1038/nmeth.2688
Badis, G. et al. Diversity and complexity in DNA recognition by transcription factors. Science 324, 1720–1723 (2009).
pubmed: 19443739
pmcid: 2905877
doi: 10.1126/science.1162327
Ciucci, T. et al. The emergence and functional fitness of memory CD4
pubmed: 30638736
pmcid: 6503975
doi: 10.1016/j.immuni.2018.12.019
Machanick, P. & Bailey, T. L. MEME-ChIP: motif analysis of large DNA datasets. Bioinformatics 27, 1696–1697 (2011).
pubmed: 21486936
pmcid: 3106185
doi: 10.1093/bioinformatics/btr189
Egawa, T. & Littman, D. R. ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat. Immunol. 9, 1131–1139 (2008).
pubmed: 18776905
pmcid: 2666788
doi: 10.1038/ni.1652
Naoe, Y. et al. Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer. J. Exp. Med. 204, 1749–1755 (2007).
pubmed: 17646405
pmcid: 2118685
doi: 10.1084/jem.20062456
Powrie, F., Leach, M. W., Mauze, S., Caddle, L. B. & Coffman, R. L. Phenotypically distinct subsets of CD4
pubmed: 7903159
doi: 10.1093/intimm/5.11.1461
DiSpirito, J. R. et al. Molecular diversification of regulatory T cells in nonlymphoid tissues. Sci. Immunol. 3, eaat5861 (2018).
pubmed: 30217811
pmcid: 6219455
doi: 10.1126/sciimmunol.aat5861
Delacher, M. et al. Precursors for nonlymphoid-tissue Treg cells reside in secondary lymphoid organs and are programmed by the transcription factor BATF. Immunity 52, 295–312 (2020).
pubmed: 31924477
pmcid: 7026712
doi: 10.1016/j.immuni.2019.12.002
Samstein, R. M. et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 151, 153–166 (2012).
pubmed: 23021222
pmcid: 3493256
doi: 10.1016/j.cell.2012.06.053
Bruno, L. et al. Runx proteins regulate Foxp3 expression. J. Exp. Med. 206, 2329–2337 (2009).
pubmed: 19841090
pmcid: 2768863
doi: 10.1084/jem.20090226
Kitoh, A. et al. Indispensable role of the Runx1-Cbfβ transcription complex for in vivo-suppressive function of FoxP3
pubmed: 19800266
doi: 10.1016/j.immuni.2009.09.003
Klunker, S. et al. Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3
pubmed: 19917773
pmcid: 2806624
doi: 10.1084/jem.20090596
Carpenter, A. C. et al. Control of regulatory T cell differentiation by the transcription factors Thpok and LRF. J. Immunol. 199, 1716–1728 (2017).
pubmed: 28754678
doi: 10.4049/jimmunol.1700181
Kanamori, M., Nakatsukasa, H., Okada, M., Lu, Q. & Yoshimura, A. Induced regulatory T cells: their development, stability, and applications. Trends Immunol. 37, 803–811 (2016).
pubmed: 27623114
doi: 10.1016/j.it.2016.08.012
Masopust, D. & Soerens, A. G. Tissue-resident T cells and other resident leukocytes. Annu. Rev. Immunol. 37, 521–546 (2019).
pubmed: 30726153
pmcid: 7175802
doi: 10.1146/annurev-immunol-042617-053214
Fonseca, R. et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. Nat. Immunol. 21, 412–421 (2020).
pubmed: 32066954
pmcid: 7096285
doi: 10.1038/s41590-020-0607-7
Gebhardt, T. et al. Different patterns of peripheral migration by memory CD4
pubmed: 21841802
doi: 10.1038/nature10339
Ricardo-Gonzalez, R. R. et al. Tissue signals imprint ILC2 identity with anticipatory function. Nat. Immunol. 19, 1093–1099 (2018).
pubmed: 30201992
pmcid: 6202223
doi: 10.1038/s41590-018-0201-4
Cohen, M. et al. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175, 1031–1044.e18 (2018).
pubmed: 30318149
doi: 10.1016/j.cell.2018.09.009
Chassaing, B. et al. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation. PloS ONE 7, e44328 (2012).
pubmed: 22957064
pmcid: 3434182
doi: 10.1371/journal.pone.0044328
Boyman, O., Kovar, M., Rubinstein, M. P., Surh, C. D. & Sprent, J. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311, 1924–1927 (2006).
pubmed: 16484453
doi: 10.1126/science.1122927
Webster, K. E. et al. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J. Exp. Med. 206, 751–760 (2009).
pubmed: 19332874
pmcid: 2715127
doi: 10.1084/jem.20082824
Trombetta, J. J. et al. Preparation of single-cell RNA-seq libraries for next generation sequencing. Curr. Protoc. Mol. Biol. 107, 4.22.1–4.22.17 (2014).
doi: 10.1002/0471142727.mb0422s107
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902.e21 (2019).
pubmed: 31178118
pmcid: 6687398
doi: 10.1016/j.cell.2019.05.031
Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).
pubmed: 27207943
doi: 10.1093/bioinformatics/btw313
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
pubmed: 30787437
pmcid: 6434952
doi: 10.1038/s41586-019-0969-x
Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).
pubmed: 29914354
pmcid: 6007078
doi: 10.1186/s12864-018-4772-0
Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525–527 (2016).
pubmed: 27043002
doi: 10.1038/nbt.3519
Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766–D773 (2019).
pubmed: 30357393
doi: 10.1093/nar/gky955
Pimentel, H., Bray, N. L., Puente, S., Melsted, P. & Pachter, L. Differential analysis of RNA-seq incorporating quantification uncertainty. Nat. Methods 14, 687–690 (2017).
pubmed: 28581496
doi: 10.1038/nmeth.4324
R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2020).
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007
Sergushichev, S. A. An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation. Preprint at bioRxiv https://doi.org/10.1101/060012 (2016).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286
pmcid: 3322381
doi: 10.1038/nmeth.1923
Fornes, O. et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 48, D87–D92 (2020).
pubmed: 31701148
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
pubmed: 20513432
pmcid: 2898526
doi: 10.1016/j.molcel.2010.05.004
Bailey, T. L. & Machanick, P. Inferring direct DNA binding from ChIP–seq. Nucleic Acids Res. 40, e128 (2012).
pubmed: 22610855
pmcid: 3458523
doi: 10.1093/nar/gks433
Jolma, A. et al. DNA-binding specificities of human transcription factors. Cell 152, 327–339 (2013).
pubmed: 23332764
doi: 10.1016/j.cell.2012.12.009
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943
pmcid: 2723002
doi: 10.1093/bioinformatics/btp352