Edozie, F. C. et al. Regulatory T-cell therapy in the induction of transplant tolerance: the issue of subpopulations. Transplantation 98, 370–379 (2014).
Sakaguchi, S., Wing, K., Onishi, Y., Prieto-Martin, P. & Yamaguchi, T. Regulatory T cells: How do they suppress immune responses? Int. Immunol. 21, 1105–1111 (2009).
Roychoudhuri, R. et al. BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis. Nature 498, 506–510 (2013).
Yadav, M. et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J. Exp. Med. 209, 1713–1722 (2012).
Thornton, A. M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441 (2010).
Floess, S. et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38 (2007).
Ohkura, N. et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 37, 785–799 (2012).
Polansky, J. K. et al. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38, 1654–1663 (2008).
Shih, H.-Y. et al. Transcriptional and epigenetic networks of helper T and innate lymphoid cells. Immunol. Rev. 261, 23–49 (2014).
Oldenhove, G. et al. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31, 772–786 (2009).
Chaudhry, A. et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986–991 (2009).
Zheng, Y. et al. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses. Nature 458, 351–356 (2009).
Koch, M. A. et al. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10, 595–602 (2009).
Wohlfert, E. A. et al. GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. J. Clin. Invest. 121, 4503–4515 (2011).
Yu, F., Sharma, S., Edwards, J., Feigenbaum, L. & Zhu, J. Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance. Nat. Immunol. 16, 197–206 (2015).
Kordasti, S. et al. Deep phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment. Blood 128, 1193–1205 (2016).
Miyara, M. et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30, 899–911 (2009).
Booth, N. J. et al. Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J. Immunol. 184, 4317–4326 (2010).
Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).
Povoleri, G. A. M. et al. Thymic versus induced regulatory T cells—Who regulates the regulators. Front. Immunol. 4, 169 (2013).
Maloy, K. J. et al. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197, 111–119 (2003).
Maul, J. et al. Peripheral and intestinal regulatory CD4+CD25(high) T cells in inflammatory bowel disease. Gastroenterology 128, 1868–1878 (2005).
Afzali, B. et al. CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner. Eur. J. Immunol. 43, 2043–2054 (2013).
Lanier, L. L., Chang, C. & Phillips, J. H. Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J. Immunol. 153, 2417–2428 (1994).
Fergusson, J. R. et al. CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages. Cell Rep. 9, 1075–1088 (2014).
Cosmi, L. et al. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J. Exp. Med. 205, 1903–1916 (2008).
Germain, C. et al. Induction of lectin-like transcript 1 (LLT1) protein cell surface expression by pathogens and interferon-γ contributes to modulate immune responses. J. Biol. Chem. 286, 37964–37975 (2011).
Wolfkamp, S. C. S. et al. Single nucleotide polymorphisms in C-type lectin genes, clustered in the IBD2 and IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory bowel diseases. Eur. J. Gastroenterol. Hepatol. 24, 965–970 (2012).
Diggins, K. E., Ferrell, P. B. & Irish, J. M. Methods for discovery and characterization of cell subsets in high dimensional mass cytometry data. Methods 82, 55–63 (2015).
Qiu, P. et al. Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE. Nat. Biotechnol. 29, 886–891 (2011).
Thomas, S. Y. et al. CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J. Immunol. 171, 2571–2580 (2003).
Venturi, V. et al. Method for assessing the similarity between subsets of the T cell receptor repertoire. J. Immunol. Methods 329, 67–80 (2008).
Ferraro, A. et al. Interindividual variation in human T regulatory cells. Proc. Natl Acad. Sci. USA 111, E1111–E1120 (2014).
Kim, Y. C. et al. Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood 119, 2810–2818 (2012).
Scotta, C. et al. Differential effects of rapamycin and retinoic acid on expansion, stability and suppressive qualities of human CD4+CD25+FOXP3+ T regulatory cell subpopulations. Haematologica 98, 1291–1299 (2013).
Afzali, B. et al. Comparison of regulatory T cells in hemodialysis patients and healthy controls: implications for cell therapy in transplantation. Clin. J. Am. Soc. Nephrol. 8, 1396–1405 (2013).
Thornton, A. M. & Shevach, E. M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287–296 (1998).
Cao, X. et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 27, 635–646 (2007).
Rosen, D. B. et al. Functional consequences of interactions between human NKR-P1A and its ligand LLT1 expressed on activated dendritic cells and B cells. J. Immunol. 180, 6508–6517 (2008).
Kitoh, A. et al. Indispensable role of the Runx1-Cbfβ transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells. Immunity 31, 609–620 (2009).
Ciofani, M. et al. A validated regulatory network for Th17 cell specification. Cell 151, 289–303 (2012).
Afzali, B. et al. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat. Immunol. 18, 813–823 (2017).
Hong, S. N. et al. RNA-seq reveals transcriptomic differences in inflamed and noninflamed intestinal mucosa of Crohn’s disease patients compared with normal mucosa of healthy controls. Inflamm. Bowel Dis. 23, 1098–1108 (2017).
Sefik, E. et al. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 349, 993–997 (2015).
Kim, B.-S. et al. Generation of RORγt+ antigen-specific T regulatory 17 cells from Foxp3+ precursors in autoimmunity. Cell Rep. 21, 195–207 (2017).
Hovhannisyan, Z., Treatman, J., Littman, D. R. & Mayer, L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 140, 957–965 (2011).
Blatner, N. R. et al. Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer. Sci. Trans. Med. 4, 164ra159 (2012).
Komatsu, N. et al. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat. Med. 20, 62–68 (2014).
Yang, B.-H. et al. Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol 9, 444–457 (2016).
Nosbaum, A. et al. Cutting edge: regulatory T cells facilitate cutaneous wound healing. J. Immunol. 196, 2010–2014 (2016).
O’Connor, W. et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat. Immunol. 10, 603–609 (2009).
Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693–1700 (2012).
Lindemans, C. A. et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528, 560–564 (2015).
Zenewicz, L. A. et al. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29, 947–957 (2008).
Amir, E.-A. D. et al. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotechnol. 31, 545–552 (2013).
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).
Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H. & Tomic-Canic, M. Growth factors and cytokines in wound healing. Wound Repair Regen. 16, 585–601 (2008).
Deonarine, K. et al. Gene expression profiling of cutaneous wound healing. J. Transl. Med. 5, 11 (2007).
Peake, M. A. et al. Identification of a transcriptional signature for the wound healing continuum. Wound Repair Regen. 22, 399–405 (2014).
Zheng, G. X. Y. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
Gong, W., Kwak, I.-Y., Pota, P., Koyano-Nakagawa, N. & Garry, D. J. DrImpute: imputing dropout events in single cell RNA sequencing data. BMC Bioinformatics 19, 220 (2018).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
Zheng, Y. et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808–812 (2010).
Robins, H. S. et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood 114, 4099–4107 (2009).
Carlson, C. S. et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat. Commun. 4, 2680 (2013).
Mathelier, A. et al. JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 44, D110–D115 (2016).
Rovedatti, L. et al. Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut 58, 1629–1636 (2009).
Cooke, K. R. et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood 88, 3230–3239 (1996).
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).
Shih, H.-Y. et al. Developmental acquisition of regulomes underlies innate lymphoid cell functionality. Cell 165, 1120–1133 (2016).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
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).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Ye, T. et al. seqMINER: an integrated ChIP-seq data interpretation platform. Nucleic Acids Res. 39, e35 (2011).
Häsler, R. et al. Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease. Gut 66, 2087–2097 (2016).