Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions

Nature Communications

Volumn 10, Issue 1, 2019, Pages

  Gutierrez Arcelus, Maria ^a,b   Teslovich, Nikola ^a,b   Mola, Alex R ^a   Polidoro, Rafael B ^a   Nathan, Aparna ^a,b   Kim, Hyun ^a,b   Hannes, Susan ^a,b   Slowikowski, Kamil ^a,b   Watts, Gerald F M ^a   Korsunsky, Ilya ^a,b   Brenner, Michael B ^a   Raychaudhuri, Soumya ^a,b,c   Brennan, Patrick J ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 18; RNA; TRANSCRIPTION FACTOR;

ADULT; ARTICLE; CD8+ T LYMPHOCYTE; CELL HETEROGENEITY; CONTROLLED STUDY; CYTOKINE RELEASE; FLOW CYTOMETRY; HUMAN; IMMUNOPHENOTYPING; LYMPHOCYTE PROLIFERATION; MUCOSAL-ASSOCIATED INVARIANT T CELL; NATURAL KILLER T CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; RNA SEQUENCE; TRANSCRIPTION REGULATION; CELL PROLIFERATION; FEMALE; GENE ONTOLOGY; INNATE IMMUNITY; LYMPHOCYTE; LYMPHOCYTE ACTIVATION; MALE; METABOLISM; MONONUCLEAR CELL; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION;

CELL PROLIFERATION; FEMALE; GENE ONTOLOGY; HUMANS; IMMUNITY, INNATE; IMMUNOPHENOTYPING; LEUKOCYTES, MONONUCLEAR; LYMPHOCYTE ACTIVATION; LYMPHOCYTES; MALE; NATURAL KILLER T-CELLS; T-LYMPHOCYTE SUBSETS;

EID: 85061273486     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-019-08604-4     Document Type: Article

References (70)

1. Godfrey, D. I., Uldrich, A. P., McCluskey, J., Rossjohn, J. & Moody, D. B. The burgeoning family of unconventional T cells. Nat. Immunol. 16, 1114–1123 (2015)
2. Van Rhijn, I. & Moody, D. B. Donor unrestricted T cells: a shared human T cell response. J. Immunol. 195, 1927–1932 (2015)
3. Brennan, P. J., Brigl, M. & Brenner, M. B. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat. Rev. Immunol. 13, 101–117 (2013)
4. Kjer-Nielsen, L. et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491, 717–723 (2012)
5. Vavassori, S. et al. Butyrophilin 3A1 binds phosphorylated antigens and stimulates human gammadelta T cells. Nat. Immunol. 14, 908–916 (2013)
6. Wang, H. et al. Butyrophilin 3A1 plays an essential role in prenyl pyrophosphate stimulation of human Vgamma2Vdelta2 T cells. J. Immunol. 191, 1029–1042 (2013)
7. Hayday, A. & Vantourout, P. A long-playing CD about the gammadelta TCR repertoire. Immunity 39, 994–996 (2013)
8. Brigl, M., Bry, L., Kent, S. C., Gumperz, J. E. & Brenner, M. B. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat. Immunol. 4, 1230–1237 (2003)
9. Ussher, J. E. et al. CD161 + + CD8 + T cells, including the MAIT cell subset, are specifically activated by IL-12 + IL-18 in a TCR-independent manner. Eur. J. Immunol. 44, 195–203 (2014)
10. Cesano, A., Visonneau, S., Clark, S. C. & Santoli, D. Cellular and molecular mechanisms of activation of MHC nonrestricted cytotoxic cells by IL-12. J. Immunol. 151, 2943–2957 (1993)
11. Novak, J., Dobrovolny, J., Novakova, L. & Kozak, T. The decrease in number and change in phenotype of mucosal-associated invariant T cells in the elderly and differences in men and women of reproductive age. Scand. J. Immunol. 80, 271–275 (2014)
12. Patin, E. et al. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nat. Immunol. 19, 302–314 (2018)
13. O’Neill, L. A., Kishton, R. J. & Rathmell, J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16, 553–565 (2016)
14. van Riggelen, J., Yetil, A. & Felsher, D. W. MYC as a regulator of ribosome biogenesis and protein synthesis. Nat. Rev. Cancer 10, 301–309 (2010)
15. Milne, A. N., Mak, W. W. & Wong, J. T. Variation of ribosomal proteins with bacterial growth rate. J. Bacteriol. 122, 89–92 (1975)
16. Bosdriesz, E., Molenaar, D., Teusink, B. & Bruggeman, F. J. How fast-growing bacteria robustly tune their ribosome concentration to approximate growth-rate maximization. Febs. J. 282, 2029–2044 (2015)
17. David, A. et al. RNA binding targets aminoacyl-tRNA synthetases to translating ribosomes. J. Biol. Chem. 286, 20688–20700 (2011)
18. Kim, H. Y. et al. The development of airway hyperreactivity in T-bet-deficient mice requires CD1d-restricted NKT cells. J. Immunol. 182, 3252–3261 (2009)
19. Szabo, S. J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655–669 (2000)
20. Albrecht, I. et al. Persistence of effector memory Th1 cells is regulated by Hopx. Eur. J. Immunol. 40, 2993–3006 (2010)
21. Dominguez, C. X. et al. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J. Exp. Med. 212, 2041–2056 (2015)
22. Omilusik, K. D. et al. Transcriptional repressor ZEB2 promotes terminal differentiation of CD8 + effector and memory T cell populations during infection. J. Exp. Med. 212, 2027–2039 (2015)
23. Weber, B. N. et al. A critical role for TCF-1 in T-lineage specification and differentiation. Nature 476, 63–68 (2011)
24. D’Cruz, L. M., Stradner, M. H., Yang, C. Y. & Goldrath, A. W. E and Id proteins influence invariant NKT cell sublineage differentiation and proliferation. J. Immunol. 192, 2227–2236 (2014)
25. Kanda, M. et al. Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-gamma production in iNKT cells. Proc. Natl Acad. Sci. USA 113, E3394–E3402 (2016)
26. Lawson, V. J., Maurice, D., Silk, J. D., Cerundolo, V. & Weston, K. Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. J. Immunol. 183, 2575–2584 (2009)
27. Monticelli, L. A. et al. Transcriptional regulator Id2 controls survival of hepatic NKT cells. Proc. Natl Acad. Sci. USA 106, 19461–19466 (2009)
28. Verykokakis, M. et al. Essential functions for ID proteins at multiple checkpoints in invariant NKT cell development. J. Immunol. 191, 5973–5983 (2013)
29. Spits, H. & Di Santo, J. P. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat. Immunol. 12, 21–27 (2011)
30. Stradner, M. H., Cheung, K. P., Lasorella, A., Goldrath, A. W. & D’Cruz, L. M. Id2 regulates hyporesponsive invariant natural killer T cells. Immunol. Cell Biol. 94, 640–645 (2016)
31. Mowel, W. K. et al. Group 1 innate lymphoid cell lineage identity is determined by a cis-regulatory element marked by a long non-coding RNA. Immunity 47, 435–449 (2017)
32. Masson, F. et al. Id2-mediated inhibition of E2A represses memory CD8 + T cell differentiation. J. Immunol. 190, 4585–4594 (2013)
33. Delconte, R. B. et al. The helix-loop-helix protein ID2 governs NK cell fate by tuning their sensitivity to interleukin-15. Immunity 44, 103–115 (2016)
34. Kovalovsky, D. et al. The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat. Immunol. 9, 1055–1064 (2008)
35. Savage, A. K. et al. The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity 29, 391–403 (2008)
36. Constantinides, M. G., McDonald, B. D., Verhoef, P. A. & Bendelac, A. A committed precursor to innate lymphoid cells. Nature 508, 397–401 (2014)
37. Eidson, M. et al. Altered development of NKT cells, gammadelta T cells, CD8 T cells and NK cells in a PLZF deficient patient. PLoS ONE 6, e24441 (2011)
38. Mao, A. P. et al. Multiple layers of transcriptional regulation by PLZF in NKT-cell development. Proc. Natl Acad. Sci. USA 113, 7602–7607 (2016)
39. Duffield, G. E. et al. A role for Id2 in regulating photic entrainment of the mammalian circadian system. Curr. Biol. 19, 297–304 (2009)
40. Honma, S. et al. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature 419, 841–844 (2002)
41. Ward, S. M., Fernando, S. J., Hou, T. Y. & Duffield, G. E. The transcriptional repressor ID2 can interact with the canonical clock components CLOCK and BMAL1 and mediate inhibitory effects on mPer1 expression. J. Biol. Chem. 285, 38987–39000 (2010)
42. Mangan, B. A. et al. Cutting edge: CD1d restriction and Th1/Th2/Th17 cytokine secretion by human Vdelta3 T cells. J. Immunol. 191, 30–34 (2013)
43. Pellicci, D. G. et al. The molecular bases of delta/alphabeta T cell-mediated antigen recognition. J. Exp. Med. 211, 2599–2615 (2014)
44. Kawabe, T. et al. Memory-phenotype CD4(+) T cells spontaneously generated under steady-state conditions exert innate TH1-like effector function. Science Immunol. 2, eaam9304 (2017)
45. Hertoghs, K. M. et al. Molecular profiling of cytomegalovirus-induced human CD8 + T cell differentiation. J. Clin. Invest. 120, 4077–4090 (2010)
46. Ranzani, V. et al. The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nat. Immunol. 16, 318–325 (2015)
47. Fonseka, C. Y. et al. Mixed-effects association of single cells identifies an expanded effector CD4(+) T cell subset in rheumatoid arthritis. Sci. Transl. Med. 10, eaaq0305 (2018)
48. Ermann, J., Rao, D. A., Teslovich, N. C., Brenner, M. B. & Raychaudhuri, S. Immune cell profiling to guide therapeutic decisions in rheumatic diseases. Nat. Rev. Rheumatol. 11, 541–551 (2015)
49. Azizi, E. et al. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174, 1293–1308 e1236 (2018)
50. Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865–868 (2017)
51. Hicks, S. C., Townes, F. W., Teng, M. & Irizarry, R. A. Missing data and technical variability in single-cell RNA-sequencing experiments. Biostatistics 19, 562–578 (2018)
52. Davey, M. S. et al. Clonal selection in the human Vdelta1 T cell repertoire indicates gammadelta TCR-dependent adaptive immune surveillance. Nat. Commun. 8, 14760 (2017)
53. Ravens, S. et al. Human gammadelta T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection. Nat. Immunol. 18, 393–401 (2017)
54. Kaech, S. M., Hemby, S., Kersh, E. & Ahmed, R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111, 837–851 (2002)
55. Liu, Y., Zhou, J. & White, K. P. RNA-seq differential expression studies: more sequence or more replication? Bioinformatics 30, 301–304 (2014)
56. Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014)
57. Stoeckius, M. et al. Cell hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018)
58. Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525–527 (2016)
59. Haghverdi, L., Lun, A. T. L., Morgan, M. D. & Marioni, J. C. Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors. Nat. Biotechnol. 36, 421–427 (2018)
60. Kiselev, V. Y., Yiu, A. & Hemberg, M. scmap: projection of single-cell RNA-seq data across data sets. Nat. Methods 15, 359–362 (2018)
61. Baglama, J. & Reichel, L. Augmented implicitly restarted Lanczos Bidiagonalization methods. SIAM J. Sci. Comput. 27, 19–42 (2005)
62. McInnes, M. & Healy, J. UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. Preprint at https://arxiv.org/abs/1802.03426 (2018)
63. 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)
64. The Gene Ontology Consortium. Expansion of the gene ontology knowledgebase and resources. Nucleic Acids Res. 45, D331-D338 (2017)
65. Ashburner, M. et al. Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25–29 (2000)
66. Eden, E., Lipson, D., Yogev, S. & Yakhini, Z. Discovering motifs in ranked lists of DNA sequences. PLoS Comput. Biol. 3, e39 (2007)
67. Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30 (2000)
68. Kamburov, A., Wierling, C., Lehrach, H. & Herwig, R. ConsensusPathDB--a database for integrating human functional interaction networks. Nucleic Acids Res. 37, D623–D628 (2009)
69. Smedley, D. et al. The BioMart community portal: an innovative alternative to large, centralized data repositories. Nucleic Acids Res. 43, W589–W598 (2015)
70. Cohen, N. R. et al. Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat. Immunol. 14, 90–99 (2013)