TLR8 escapes X chromosome inactivation in human monocytes and CD4
Human monocytes and CD4+ T cells
Klinefelter syndrome
Toll-like receptor 7
Toll-like receptor 8
X chromosome inactivation escape
Journal
Biology of sex differences
ISSN: 2042-6410
Titre abrégé: Biol Sex Differ
Pays: England
ID NLM: 101548963
Informations de publication
Date de publication:
18 09 2023
18 09 2023
Historique:
received:
19
01
2023
accepted:
04
09
2023
medline:
20
9
2023
pubmed:
19
9
2023
entrez:
18
9
2023
Statut:
epublish
Résumé
Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that TLR7 evades X chromosome inactivation (XCI) in female immune cells. Whether TLR8 also evades XCI, however, has not yet been explored. In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of TLR7 and TLR8 relative to X chromosome territories in CD14 Using RNA FISH, we show that TLR8, like TLR7, evades XCI in immune cells, and that cells harboring simultaneously TLR7 and TLR8 transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency. This transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells. TLR8, mirroring TLR7, escapes XCI in human monocytes and CD4 Human endosomal Toll-like receptors TLR7 and TLR8, encoded by two adjacent X-linked genes, recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. We previously reported that TLR7 evades X chromosome inactivation (XCI) in female immune cells, correlating with enhanced functional properties in B cells harboring biallelic expression of this gene. Here, we conducted a comprehensive single-cell resolution analysis of the transcriptional regulation of both TLR7 and TLR8, in CD14
Sections du résumé
BACKGROUND
Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that TLR7 evades X chromosome inactivation (XCI) in female immune cells. Whether TLR8 also evades XCI, however, has not yet been explored.
METHOD
In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of TLR7 and TLR8 relative to X chromosome territories in CD14
RESULTS
Using RNA FISH, we show that TLR8, like TLR7, evades XCI in immune cells, and that cells harboring simultaneously TLR7 and TLR8 transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency. This transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells.
CONCLUSIONS
TLR8, mirroring TLR7, escapes XCI in human monocytes and CD4
Human endosomal Toll-like receptors TLR7 and TLR8, encoded by two adjacent X-linked genes, recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. We previously reported that TLR7 evades X chromosome inactivation (XCI) in female immune cells, correlating with enhanced functional properties in B cells harboring biallelic expression of this gene. Here, we conducted a comprehensive single-cell resolution analysis of the transcriptional regulation of both TLR7 and TLR8, in CD14
Autres résumés
Type: plain-language-summary
(eng)
Human endosomal Toll-like receptors TLR7 and TLR8, encoded by two adjacent X-linked genes, recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. We previously reported that TLR7 evades X chromosome inactivation (XCI) in female immune cells, correlating with enhanced functional properties in B cells harboring biallelic expression of this gene. Here, we conducted a comprehensive single-cell resolution analysis of the transcriptional regulation of both TLR7 and TLR8, in CD14
Identifiants
pubmed: 37723501
doi: 10.1186/s13293-023-00544-5
pii: 10.1186/s13293-023-00544-5
pmc: PMC10506212
doi:
Substances chimiques
Toll-Like Receptor 8
0
Toll-Like Receptor 7
0
TLR8 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
60Informations de copyright
© 2023. Society for Women's Health Research and BioMed Central Ltd.
Références
Beignon A-S, McKenna K, Skoberne M, Manches O, DaSilva I, Kavanagh DG, et al. Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor–viral RNA interactions. J Clin Invest. 2005;115(11):3265–75.
pubmed: 16224540
pmcid: 1253628
Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303(5663):1529–31.
pubmed: 14976261
Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science. 2004;303(5663):1526–9.
pubmed: 14976262
Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA. 2004;101(15):5598–603.
pubmed: 15034168
pmcid: 397437
Melchjorsen J, Jensen Søren B, Malmgaard L, Rasmussen Simon B, Weber F, Bowie Andrew G, et al. Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J Virol. 2005;79(20):12944–51.
pubmed: 16188996
pmcid: 1235860
Greulich W, Wagner M, Gaidt MM, Stafford C, Cheng Y, Linder A, et al. TLR8 is a sensor of RNase T2 degradation products. Cell. 2019;179(6):1264-75 e13.
pubmed: 31778653
pmcid: 7116005
Ugolini M, Gerhard J, Burkert S, Jensen KJ, Georg P, Ebner F, et al. Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses. Nat Immunol. 2018;19(4):386–96.
pubmed: 29556002
Caetano BC, Carmo BB, Melo MB, Cerny A, dos Santos SL, Bartholomeu DC, et al. Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi. J Immunol. 2011;187(4):1903–11.
pubmed: 21753151
Biondo C, Malara A, Costa A, Signorino G, Cardile F, Midiri A, et al. Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis. Eur J Immunol. 2012;42(10):2632–43.
pubmed: 22777843
Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, et al. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med. 2005;202(8):1131–9.
pubmed: 16230478
pmcid: 2213213
Shibata T, Ohto U, Nomura S, Kibata K, Motoi Y, Zhang Y, et al. Guanosine and its modified derivatives are endogenous ligands for TLR7. Int Immunol. 2016;28(5):211–22.
pubmed: 26489884
Barrat FJ, Elkon KB, Fitzgerald KA. Importance of nucleic acid recognition in inflammation and autoimmunity. Annu Rev Med. 2016;67:323–36.
pubmed: 26526766
Shimizu T. Structural insights into ligand recognition and regulation of nucleic acid-sensing Toll-like receptors. Curr Opin Struct Biol. 2017;47:52–9.
pubmed: 28600980
Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, et al. Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat Struct Mol Biol. 2015;22(2):109–15.
pubmed: 25599397
Zhang Z, Ohto U, Shibata T, Krayukhina E, Taoka M, Yamauchi Y, et al. Structural analysis reveals that toll-like receptor 7 is a dual receptor for guanosine and single-stranded RNA. Immunity. 2016;45(4):737–48.
pubmed: 27742543
Guiducci C, Gong M, Cepika AM, Xu Z, Tripodo C, Bennett L, et al. RNA recognition by human TLR8 can lead to autoimmune inflammation. J Exp Med. 2013;210(13):2903–19.
pubmed: 24277153
pmcid: 3865472
Hornung V, Barchet W, Schlee M, Hartmann G. RNA recognition via TLR7 and TLR8. In: Bauer S, Hartmann G, editors. Toll-like receptors (TLRs) and innate immunity, handbook of experimental pharmacology. Berlin: Springer; 2008. p. 71–86.
Dominguez-Villar M, Gautron AS, de Marcken M, Keller MJ, Hafler DA. TLR7 induces anergy in human CD4(+) T cells. Nat Immunol. 2015;16(1):118–28.
pubmed: 25401424
Fabié A, Mai LT, Dagenais-Lussier X, Hammami A, van Grevenynghe J, Stäger S. IRF-5 promotes cell death in CD4 T cells during chronic infection. Cell Rep. 2018;24(5):1163–75.
pubmed: 30067973
Li L, Liu X, Sanders KL, Edwards JL, Ye J, Si F, et al. TLR8-mediated metabolic control of human Treg function: a mechanistic target for cancer immunotherapy. Cell Metab. 2019;29(1):103-23 e5.
pubmed: 30344014
Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, et al. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science. 2005;309(5739):1380–4.
pubmed: 16123302
Salvi V, Nguyen HO, Sozio F, Schioppa T, Gaudenzi C, Laffranchi M, et al. SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8. JCI Insight. 2021;6(18): e150542.
pubmed: 34375313
pmcid: 8492321
Laurent P, Yang C, Rendeiro AF, Nilsson-Payant BE, Carrau L, Chandar V, et al. Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19. Sci Immunol. 2022;7(75):eadd4906.
pubmed: 36083891
pmcid: 9853436
Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, et al. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 2009;5(7): e1000562.
pubmed: 19609346
pmcid: 2702086
van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, et al. Presence of genetic variants among young men with severe COVID-19. JAMA. 2020;324(7):663–73.
pubmed: 32706371
Fallerini C, Daga S, Mantovani S, Benetti E, Picchiotti N, Francisci D, et al. Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study. Elife. 2021;10: e67569.
pubmed: 33650967
pmcid: 7987337
Kosmicki JA, Horowitz JE, Banerjee N, Lanche R, Marcketta A, Maxwell E, et al. Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals. Am J Hum Genet. 2021;108(7):1350–5.
pubmed: 34115965
Solanich X, Vargas-Parra G, van der Made CI, Simons A, Schuurs-Hoeijmakers J, Antolí A, et al. Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19. Front Immunol. 2021;12:719115.
pubmed: 34367187
pmcid: 8343010
Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol. 2021;6(62):eabl4348.
pubmed: 34413140
pmcid: 8532080
Lind NA, Rael VE, Pestal K, Liu B, Barton GM. Regulation of the nucleic acid-sensing Toll-like receptors. Nat Rev Immunol. 2022;22(4):224–35.
pubmed: 34272507
Sharma S, Fitzgerald KA, Cancro MP, Marshak-Rothstein A. Nucleic acid-sensing receptors: rheostats of autoimmunity and autoinflammation. J Immunol. 2015;195(8):3507–12.
pubmed: 26432899
Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006;312(5780):1669–72.
pubmed: 16709748
Deane JA, Pisitkun P, Barrett RS, Feigenbaum L, Town T, Ward JM, et al. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity. 2007;27(5):801–10.
pubmed: 17997333
pmcid: 2706502
Ricker E, Manni M, Flores-Castro D, Jenkins D, Gupta S, Rivera-Correa J, et al. Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice. Nat Commun. 2021;12(1):4813.
pubmed: 34376664
pmcid: 8355159
Berland R, Fernandez L, Kari E, Han J-H, Lomakin I, Akira S, et al. Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice. Immunity. 2006;25(3):429–40.
pubmed: 16973388
Christensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Shlomchik MJ. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity. 2006;25(3):417–28.
pubmed: 16973389
Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, et al. TLR8 deficiency leads to autoimmunity in mice. J Clin Invest. 2010;120(10):3651–62.
pubmed: 20811154
pmcid: 2947223
Desnues B, Macedo AB, Roussel-Queval A, Bonnardel J, Henri S, Demaria O, et al. TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc Natl Acad Sci USA. 2014;111(4):1497–502.
pubmed: 24474776
pmcid: 3910605
Brown GJ, Cañete PF, Wang H, Medhavy A, Bones J, Roco JA, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;605(7909):349–56.
pubmed: 35477763
pmcid: 9095492
Fejtkova M, Sukova M, Hlozkova K, Skvarova Kramarzova K, Rackova M, Jakubec D, et al. TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins. Am J Hematol. 2022;97(3):338–51.
pubmed: 34981838
Liu G, Zhang H, Zhao C, Zhang H. Evolutionary history of the Toll-like receptor gene family across vertebrates. Genome Biol Evol. 2020;12(1):3615–34.
pubmed: 31800025
Benton MJ. Vertebrate palaeontology. 4th ed. Oxford: Wiley Blackwell; 2015.
Dossin F, Heard E. The molecular and nuclear dynamics of X-chromosome inactivation. Cold Spring Harb Perspect Biol. 2022;14(4):a040196.
pubmed: 34312245
Skuse D, Printzlau F, Wolstencroft J. Sex chromosome aneuploidies. Handb Clin Neurol. 2018;147:355–76.
pubmed: 29325624
Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031):400–4.
pubmed: 15772666
Peeters SB, Cotton AM, Brown CJ. Variable escape from X-chromosome inactivation: identifying factors that tip the scales towards expression. BioEssays. 2014;36(8):746–56.
pubmed: 24913292
pmcid: 4143967
Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R, et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017;550(7675):244–8.
pubmed: 29022598
pmcid: 5685192
Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol. 2018;3(19):eaap8855.
pubmed: 29374079
Abbas F, Cenac C, Youness A, Azar P, Delobel P, Guery JC. HIV-1 infection enhances innate function and TLR7 expression in female plasmacytoid dendritic cells. Life Sci Alliance. 2022;5(10): e202201452.
pubmed: 36271499
pmcid: 9441429
Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M, et al. Klinefelter’s syndrome (47, XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum. 2008;58(8):2511–7.
pubmed: 18668569
pmcid: 2824898
Harris VM, Sharma R, Cavett J, Kurien BT, Liu K, Koelsch KA, et al. Klinefelter’s syndrome (47, XXY) is in excess among men with Sjögren’s syndrome. Clin Immunol. 2016;168:25–9.
pubmed: 27109640
pmcid: 4940221
Scofield RH, Lewis VM, Cavitt J, Kurien BT, Assassi S, Martin J, et al. 47XXY and 47XXX in scleroderma and myositis. ACR Open Rheumatol. 2022;4(6):528–33.
pubmed: 35352506
pmcid: 9190224
Caron G, Duluc D, Fremaux I, Jeannin P, David C, Gascan H, et al. Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J Immunol. 2005;175(3):1551–7.
pubmed: 16034093
de Marcken M, Dhaliwal K, Danielsen AC, Gautron AS, Dominguez-Villar M. TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection. Sci Signal. 2019;12(605):eaaw1347.
pubmed: 31662487
Meas HZ, Haug M, Beckwith MS, Louet C, Ryan L, Hu Z, et al. Sensing of HIV-1 by TLR8 activates human T cells and reverses latency. Nat Commun. 2020;11(1):147.
pubmed: 31919342
pmcid: 6952430
Azar P, Mejia JE, Cenac C, Shaiykova A, Youness A, Laffont S, et al. TLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women. JCI Insight. 2020;5(12): e136047.
pubmed: 32554924
pmcid: 7406249
Smit A, Hubley R, Green P. RepeatMasker Open-4.0 2013–2015. https://www.repeatmasker.org . Accessed 20 Feb 2020.
Greenfield A, Carrel L, Pennisi D, Philippe C, Quaderi N, Siggers P, et al. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet. 1998;7(4):737–42.
pubmed: 9499428
Chaumeil J, Augui S, Chow JC, Heard E. Combined immunofluorescence, RNA fluorescent in situ hybridization, and DNA fluorescent in situ hybridization to study chromatin changes, transcriptional activity, nuclear organization, and X-chromosome inactivation. In: Hancock R, editor. The Nucleus. 1: Nuclei and subnuclear components. Totowa: Humana Press; 2008. p. 297–308.
R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2022.
Berry KJ, Johnston JE, Mielke PW. Fourfold contingency tables, I. The measurement of association: a permutation statistical approach. Cham: Springer; 2018. p. 511–76.
Yang G, Cheng JQ, Xie M, Qian W. gmeta: meta-analysis via a unified framework of confidence distribution. R package version 2.3–1. 2021.
Xie MG, Singh K. Confidence distribution, the frequentist distribution estimator of a parameter: a review. Int Stat Rev. 2013;81(1):3–39.
Durand NC, Robinson JT, Shamim MS, Machol I, Mesirov JP, Lander ES, et al. Juicebox provides a visualization system for Hi-C contact maps with unlimited zoom. Cell Syst. 2016;3(1):99–101.
pubmed: 27467250
pmcid: 5596920
Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014;159(7):1665–80.
pubmed: 25497547
pmcid: 5635824
Phanstiel DH, Van Bortle K, Spacek D, Hess GT, Shamim MS, Machol I, et al. Static and dynamic DNA loops form AP-1-bound activation hubs during macrophage development. Mol Cell. 2017;67(6):1037-48.e6.
pubmed: 28890333
pmcid: 5610110
Zhang X, Jeong M, Huang X, Wang XQ, Wang X, Zhou W, et al. Large DNA methylation nadirs anchor chromatin loops maintaining hematopoietic stem cell identity. Mol Cell. 2020;78(3):506-21.e6.
pubmed: 32386543
pmcid: 7357281
Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289–93.
pubmed: 19815776
pmcid: 2858594
Giorgetti L, Lajoie BR, Carter AC, Attia M, Zhan Y, Xu J, et al. Structural organization of the inactive X chromosome in the mouse. Nature. 2016;535(7613):575–9.
pubmed: 27437574
pmcid: 5443622
Savarese F, Flahndorfer K, Jaenisch R, Busslinger M, Wutz A. Hematopoietic precursor cells transiently reestablish permissiveness for X inactivation. Mol Cell Biol. 2006;26(19):7167–77.
pubmed: 16980619
pmcid: 1592878
Syrett CM, Sindhava V, Hodawadekar S, Myles A, Liang G, Zhang Y, et al. Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells. PLoS Genet. 2017;13(10): e1007050.
pubmed: 28991910
pmcid: 5648283
Wang J, Syrett CM, Kramer MC, Basu A, Atchison ML, Anguera MC. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proc Natl Acad Sci USA. 2016;113(14):E2029–38.
pubmed: 27001848
pmcid: 4833277
Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, et al. Quantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002;168(9):4531–7.
pubmed: 11970999
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83.
pubmed: 15262106
Wang YL, Ni TF, Wang W, Liu F. Gene transcription in bursting: a unified mode for realizing accuracy and stochasticity. Biol Rev Camb Philos Soc. 2019;94(1):248–58.
pubmed: 30024089
Souyris M, Mejía JE, Chaumeil J, Guéry J-C. Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation. Semin Immunopathol. 2019;41(2):153–64.
pubmed: 30276444
Hagen SH, Henseling F, Hennesen J, Savel H, Delahaye S, Richert L, et al. Heterogeneous escape from X chromosome inactivation results in sex differences in type I IFN responses at the single human pDC level. Cell Rep. 2020;33(10): 108485.
pubmed: 33296655
pmcid: 7833293
Wimmers F, Subedi N, van Buuringen N, Heister D, Vivie J, Beeren-Reinieren I, et al. Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nat Commun. 2018;9(1):3317.
pubmed: 30127440
pmcid: 6102223
Gal-Oz ST, Maier B, Yoshida H, Seddu K, Elbaz N, Czysz C, et al. ImmGen report: sexual dimorphism in the immune system transcriptome. Nat Commun. 2019;10(1):4295.
pubmed: 31541153
pmcid: 6754408
Marx V. A dream of single-cell proteomics. Nat Methods. 2019;16(9):809–12.
pubmed: 31406385
Bender M, Christiansen J, Quick M. The terrible toll of 76 autoimmune diseases. Sci Am. 2021;325(3):31–3.
Dowling DJ. Recent advances in the discovery and delivery of TLR7/8 agonists as vaccine adjuvants. Immunohorizons. 2018;2(6):185–97.
pubmed: 31022686