Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits.
Adoptive Transfer
Animals
CRISPR-Cas Systems
/ genetics
Cell Differentiation
/ genetics
Cell Line
Cell Movement
/ genetics
Chromatin Immunoprecipitation Sequencing
Cytokines
/ immunology
Female
Gene Expression Regulation
/ immunology
Gene Regulatory Networks
Germinal Center
/ cytology
Humans
Male
Mice
Mutation
Promoter Regions, Genetic
/ genetics
Proto-Oncogene Proteins c-bcl-6
/ genetics
RNA-Seq
Repressor Proteins
/ genetics
Signal Transduction
/ genetics
T-Lymphocytes, Helper-Inducer
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
14
08
2019
accepted:
06
05
2020
pubmed:
24
6
2020
medline:
21
10
2020
entrez:
24
6
2020
Statut:
ppublish
Résumé
T follicular helper (T
Identifiants
pubmed: 32572238
doi: 10.1038/s41590-020-0706-5
pii: 10.1038/s41590-020-0706-5
pmc: PMC7449381
mid: NIHMS1591987
doi:
Substances chimiques
BCL6 protein, human
0
Bcl6 protein, mouse
0
Cytokines
0
Proto-Oncogene Proteins c-bcl-6
0
Repressor Proteins
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
777-789Subventions
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI072543
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027366
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109976
Pays : United States
Références
Crotty, S. T follicular helper cell biology: a decade of discovery and diseases. Immunity 50, 1132–1148 (2019).
pubmed: 31117010
pmcid: 6532429
doi: 10.1016/j.immuni.2019.04.011
Vinuesa, C. G., Linterman, M. A., Yu, D. & MacLennan, I. C. M. Follicular helper T cells. Annu. Rev. Immunol. 34, 335–368 (2016).
pubmed: 26907215
doi: 10.1146/annurev-immunol-041015-055605
Johnston, R. J. et al. Bcl6 and Blimp1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006–1010 (2009).
pubmed: 19608860
pmcid: 2766560
doi: 10.1126/science.1175870
Yu, D. et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457–468 (2009).
pubmed: 19631565
doi: 10.1016/j.immuni.2009.07.002
Nurieva, R. I. et al. Bcl6 mediates the development of T follicular helper cells. Science 325, 1001–1005 (2009).
pubmed: 19628815
pmcid: 2857334
doi: 10.1126/science.1176676
Crotty, S. T follicular helper cell differentiation, function, and roles in disease. Immunity 41, 529–542 (2014).
pubmed: 25367570
pmcid: 25367570
doi: 10.1016/j.immuni.2014.10.004
Ise, W. et al. The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat. Immunol. 12, 536–543 (2011).
pubmed: 21572431
pmcid: 3117275
doi: 10.1038/ni.2037
Kroenke, M. A. et al. Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. J. Immunol. 188, 3734–3744 (2012).
pubmed: 22427637
pmcid: 3324673
doi: 10.4049/jimmunol.1103246
Johnston, R. J., Choi, Y. S., Diamond, J. A., Yang, J. A. & Crotty, S. STAT5 is a potent negative regulator of T
pubmed: 22271576
pmcid: 3281266
doi: 10.1084/jem.20111174
Choi, Y. S., Eto, D., Yang, J. A., Lao, C. & Crotty, S. Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation. J. Immunol. 190, 3049–3053 (2013).
pubmed: 23447690
pmcid: 3626564
doi: 10.4049/jimmunol.1203032
Wang, H. et al. The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells. Nat. Immunol. 15, 667–675 (2014).
pubmed: 24859450
pmcid: 4142638
doi: 10.1038/ni.2890
Stone, E. L. et al. ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation. Immunity 42, 239–251 (2015).
pubmed: 25692700
pmcid: 4334393
doi: 10.1016/j.immuni.2015.01.017
Lee, J.-Y. et al. The transcription factor KLF2 restrains CD4
pubmed: 25692701
pmcid: 4409658
doi: 10.1016/j.immuni.2015.01.013
Weber, J. P. et al. ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2. J. Exp. Med. 212, 217–233 (2015).
pubmed: 25646266
pmcid: 4322049
doi: 10.1084/jem.20141432
Krishnamoorthy, V. et al. The IRF4 gene regulatory module functions as a read-write integrator to dynamically coordinate T helper cell fate. Immunity 47, 481–497.e7 (2017).
pubmed: 28930660
pmcid: 5661949
doi: 10.1016/j.immuni.2017.09.001
Kim, C. J. et al. The transcription factor Ets1 suppresses T follicular helper type 2 cell differentiation to halt the onset of systemic lupus erythematosus. Immunity 49, 1034–1048.e8 (2018).
pubmed: 30566881
doi: 10.1016/j.immuni.2018.10.012
Lahmann, A. et al. Bach2 controls T follicular helper cells by direct repression of Bcl-6. J. Immunol. 202, 2229–2239 (2019).
pubmed: 30833348
doi: 10.4049/jimmunol.1801400
Geng, J. et al. Bach2 negatively regulates T follicular helper cell differentiation and is critical for CD4
pubmed: 30971440
pmcid: 6504585
doi: 10.4049/jimmunol.1801626
Choi, Y. S. et al. LEF-1 and TCF-1 orchestrate T
pubmed: 26214741
pmcid: 4545301
doi: 10.1038/ni.3226
Xu, L. et al. The transcription factor TCF-1 initiates the differentiation of T
pubmed: 26214740
doi: 10.1038/ni.3229
Wu, T. et al. TCF1 is required for the T follicular helper cell response to viral infection. Cell Rep. 12, 2099–2110 (2015).
pubmed: 26365183
pmcid: 4591235
doi: 10.1016/j.celrep.2015.08.049
Shaw, L. A. et al. Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation. Nat. Immunol. 17, 834–843 (2016).
pubmed: 27213691
pmcid: 4915968
doi: 10.1038/ni.3461
Liu, X. et al. Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature 507, 513–518 (2014).
pubmed: 24463518
pmcid: 4012617
doi: 10.1038/nature12910
Hatzi, K. et al. BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms. J. Exp. Med. 212, 539–553 (2015).
pubmed: 25824819
pmcid: 4387288
doi: 10.1084/jem.20141380
Liu, X. et al. Genome-wide analysis identifies Bcl6-controlled regulatory networks during T follicular helper cell differentiation. Cell Rep. 14, 1735–1747 (2016).
pubmed: 26876184
pmcid: 4975778
doi: 10.1016/j.celrep.2016.01.038
Crotty, S., Johnston, R. J. & Schoenberger, S. P. Effectors and memories: Bcl6 and Blimp1 in T and B lymphocyte differentiation. Nat. Immunol. 11, 114–120 (2010).
pubmed: 20084069
pmcid: 2864556
doi: 10.1038/ni.1837
Crotty, S. Follicular helper CD4 T cells (T
pubmed: 21314428
doi: 10.1146/annurev-immunol-031210-101400
Nance, J. P. et al. Bcl6 middle domain repressor function is required for T follicular helper cell differentiation and utilizes the corepressor MTA3. Proc. Natl Acad. Sci. USA 112, 13324–13329 (2015).
pubmed: 26460037
doi: 10.1073/pnas.1507312112
Xie, M. M. et al. Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice. Eur. J. Immunol. 47, 1136–1141 (2017).
pubmed: 28586108
pmcid: 5578616
doi: 10.1002/eji.201747034
Mendez, L. M. et al. CtBP is an essential corepressor for BCL6 autoregulation. Mol. Cell. Biol. 28, 2175–2186 (2008).
pubmed: 18212045
pmcid: 2268420
doi: 10.1128/MCB.01400-07
Huynh, K. D. & Bardwell, V. J. The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT. Oncogene 17, 2473–2484 (1998).
pubmed: 9824158
doi: 10.1038/sj.onc.1202197
Bartfeld, D. et al. DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending. Structure 10, 1395–1407 (2002).
pubmed: 12377125
doi: 10.1016/S0969-2126(02)00853-5
Hiramatsu, Y. et al. c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-β inhibits c-Maf-induced IL-21 production in CD4
pubmed: 20042469
doi: 10.1189/jlb.0909639
Sahoo, A. et al. Batf is important for IL-4 expression in T follicular helper cells. Nat. Commun. 6, 7997 (2015).
pubmed: 26278622
pmcid: 4557271
doi: 10.1038/ncomms8997
Hatzi, K. et al. A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters. Cell Rep. 4, 578–588 (2013).
pubmed: 23911289
doi: 10.1016/j.celrep.2013.06.016
Pasqualucci, L. & Dalla Favera, R. Genetics of diffuse large B-cell lymphoma. Blood 131, 2307–2319 (2018).
pubmed: 29666115
pmcid: 5969374
doi: 10.1182/blood-2017-11-764332
Kusam, S., Toney, L. M., Sato, H. & Dent, A. L. Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. J. Immunol. 170, 2435–2441 (2003).
pubmed: 12594267
doi: 10.4049/jimmunol.170.5.2435
Kwon, H.-K., Chen, H.-M., Mathis, D. & Benoist, C. Different molecular complexes that mediate transcriptional induction and repression by FoxP3. Nat. Immunol. 486, 549–1248 (2017).
Ciofani, M. et al. A validated regulatory network for Th17 cell specification. Cell 151, 289–303 (2012).
pubmed: 23021777
pmcid: 3503487
doi: 10.1016/j.cell.2012.09.016
Iwata, S. et al. The transcription factor T-bet limits amplification of type I IFN transcriptome and circuitry in T helper 1 cells. Immunity 46, 983–991.e4 (2017).
pubmed: 28623086
pmcid: 5523825
doi: 10.1016/j.immuni.2017.05.005
Vahedi, G. et al. Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol. Rev. 252, 24–40 (2013).
pubmed: 23405893
pmcid: 3577092
doi: 10.1111/imr.12037
Mackay, L. K. et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352, 459–463 (2016).
pubmed: 27102484
doi: 10.1126/science.aad2035
Masson, F. et al. Id2-mediated inhibition of E2A represses memory CD8
pubmed: 23536629
pmcid: 3631715
doi: 10.4049/jimmunol.1300099
Oxenius, A., Bachmann, M. F., Zinkernagel, R. M. & Hengartner, H. Virus‐specific major MHC class II‐restricted TCR‐transgenic mice: effects on humoral and cellular immune responses after viral infection. Eur. J. Immunol. 28, 390–400 (1998).
pubmed: 9485218
doi: 10.1002/(SICI)1521-4141(199801)28:01<390::AID-IMMU390>3.0.CO;2-O
Kaji, T. et al. Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J. Exp. Med. 209, 2079–2097 (2012).
pubmed: 23027924
pmcid: 3478929
doi: 10.1084/jem.20120127
Shapiro-Shelef, M. et al. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19, 607–620 (2003).
pubmed: 14563324
doi: 10.1016/S1074-7613(03)00267-X
Rutishauser, R. L. et al. Transcriptional repressor Blimp-1 promotes CD8
pubmed: 19664941
pmcid: 2783637
doi: 10.1016/j.immuni.2009.05.014
Wang, D. et al. The transcription factor Runx3 establishes chromatin accessibility of cis-regulatory landscapes that drive memory cytotoxic T lymphocyte formation. Immunity 48, 659–674.e6 (2018).
pubmed: 29669249
pmcid: 6750808
doi: 10.1016/j.immuni.2018.03.028
Rosenbauer, F. et al. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat. Genet. 38, 27–37 (2006).
pubmed: 16311598
doi: 10.1038/ng1679
Montague, T. G., Cruz, J. M., Gagnon, J. A., Church, G. M. & Valen, E. CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res. 42, W401–W407 (2014).
pubmed: 24861617
pmcid: 4086086
doi: 10.1093/nar/gku410
Seumois, G. et al. Transcriptional profiling of Th2 cells identifies pathogenic features associated with asthma. J. Immunol. 197, 655–664 (2016).
pubmed: 27271570
pmcid: 4936908
doi: 10.4049/jimmunol.1600397
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289–300 (1995).
Raykov, Y. P., Boukouvalas, A., Baig, F. & Little, M. A. What to do when K-means clustering fails: a simple yet principled alternative algorithm. PLoS ONE 11, e0162259 (2016).
pubmed: 27669525
pmcid: 5036949
doi: 10.1371/journal.pone.0162259
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
doi: 10.1073/pnas.0506580102
pubmed: 16199517
Jain, R. et al. Interleukin-23-induced transcription factor Blimp-1 promotes pathogenicity of T helper 17 cells. Immunity 44, 131–142 (2016).
pubmed: 26750311
doi: 10.1016/j.immuni.2015.11.009
Yu, B. et al. Epigenetic landscapes reveal transcription factors that regulate CD8
pubmed: 28288100
pmcid: 5395420
doi: 10.1038/ni.3706
Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
pubmed: 25260700
doi: 10.1093/bioinformatics/btu638
Pedregosa, F. et al. Scikit-learn: machine learning in Python. J. Mach. Learn. Res. 12, 2825–2830 (2011).
Wingender, E., Schoeps, T., Haubrock, M., Krull, M. & Dönitz, J. TFClass: expanding the classification of human transcription factors to their mammalian orthologs. Nucleic Acids Res. 46, D343–D347 (2018).
pubmed: 29087517
doi: 10.1093/nar/gkx987
Li, Z. et al. Identification of transcription factor binding sites using ATAC-seq. Genome Biol. 20, 45 (2019).
pubmed: 30808370
pmcid: 6391789
doi: 10.1186/s13059-019-1642-2
Stormo, G. D. Modeling the specificity of protein-DNA interactions. Quant. Biol. 1, 115–130 (2013).
pubmed: 25045190
pmcid: 4101922
doi: 10.1007/s40484-013-0012-4
Li, F. et al. Ezh2 programs TFH differentiation by integrating phosphorylation-dependent activation of Bcl6 and polycomb-dependent repression of p19Arf. Nat. Commun. 9, 5452 (2018).
pubmed: 30575739
pmcid: 6303346
doi: 10.1038/s41467-018-07853-z