Peripheral immune landscape and natural killer-like B cells in human Vogt-Koyanagi-Harada disease
He Li, Lei Zhu, Xiuxing Liu, Lihui Xie, Rong Wang, Zhaohuai Li, Zhaohao Huang, Shizhao Yang, Binyao Chen, Jinguo Ye, Yingfeng Zheng, Wenru Su
Peripheral immune landscape and natural killer-like B cells in human Vogt-Koyanagi-Harada disease
Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder threatening the eyesight. The pathogenic mechanisms and biomarkers reflecting disease severity and predicting treatment response require further exploration. Here, we performed a single-cell analysis of peripheral blood mononuclear cells (PBMC) obtained from eight patients with VKH disease and eight healthy controls to comprehensively delineate the changes in VKH disease. We showed a mixture of inflammation, effector, and exhausted states for PBMCs in VKH disease. Notably, our study implicated a newly identified B cell subset, natural killer-like B cells (K-BC) characterized by expressing CD19 and CD56, was correlated with VKH disease. K-BCs expanded in VKH disease, fell back after effective treatment, and promoted the differentiation of pathogenic T cells. Overall, we mapped the peripheral immune cell atlas in VKH disease and indicated the pathogenic role and potential value in predicting treatment response of K-BCs.
Vogt-Koyanagi-Harada disease / single-cell RNA sequencing / natural killer-like B cells / autoimmunity
[1] |
Du L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res 2016;52:84–111.
CrossRef
Google scholar
|
[2] |
Read RW, Holland GN, Rao NA, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature. Am J Ophthalmol 2001;131:647–52.
CrossRef
Google scholar
|
[3] |
Hou S, Li N, Liao X, et al. Uveitis genetics. Exp Eye Res 2020;190:107853.
CrossRef
Google scholar
|
[4] |
Rao NA, Gupta A, Dustin L, et al. Frequency of distinguishing clinical features in Vogt-Koyanagi-Harada disease. Ophthalmology 2010;117:591–9, 599.e1.
CrossRef
Google scholar
|
[5] |
Yang P, Zhong Y, Du L, et al. Development and evaluation of diagnostic criteria for Vogt-Koyanagi-Harada disease. JAMA Ophthalmol 2018;136:1025–31.
CrossRef
Google scholar
|
[6] |
Abu El-Asrar AM, Van Damme J, Struyf S, et al. New perspectives on the immunopathogenesis and treatment of uveitis associated with Vogt-Koyanagi-Harada disease. Front Med 2021;8:705796.
CrossRef
Google scholar
|
[7] |
Lin P, Suhler EB, Rosenbaum JT. The future of uveitis treatment. Ophthalmology 2014;121:365–76.
CrossRef
Google scholar
|
[8] |
Uchiyama E, Papaliodis GN, Lobo AM, et al. Side-effects of anti-inflammatory therapy in uveitis. Semin Ophthalmol 2014;29:456–67.
CrossRef
Google scholar
|
[9] |
Imrie FR, Dick AD. Biologics in the treatment of uveitis. Curr Opin Ophthalmol 2007;18:481–6.
CrossRef
Google scholar
|
[10] |
Damico FM, Cunha-Neto E, Goldberg AC, et al. T-cell recognition and cytokine profile induced by melanocyte epitopes in patients with HLADRB1* 0405-positive and -negative Vogt-Koyanagi-Harada uveitis. Invest Ophthalmol Vis Sci 2005;46:2465–71.
CrossRef
Google scholar
|
[11] |
Sugita S, Takase H, Kawaguchi T, et al. Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int Ophthalmol 2007;27:87–95.
CrossRef
Google scholar
|
[12] |
Hammer H. Cellular hypersensitivity to uveal pigment confirmed by leucocyte migration tests in sympathetic ophthalmitis and the Vogt-Koyanagi-Harada syndrome. Br J Ophthalmol 1974;58:773773776–776.
CrossRef
Google scholar
|
[13] |
Zhong Z, Su G, Kijlstra A, et al. Activation of the interleukin-23/interleukin-17 signalling pathway in autoinflammatory and autoimmune uveitis. Prog Retin Eye Res 2021;80:100866.
CrossRef
Google scholar
|
[14] |
Wu S, Ma R, Zhong Y, et al. Deficiency of IL-27 signaling exacerbates experimental autoimmune uveitis with elevated uveitogenic Th1 and Th17 responses. Int J Mol Sci 2021;22:7517.
CrossRef
Google scholar
|
[15] |
Tsuruta D, Hamada T, Teramae H, et al. Inflammatory vitiligo in Vogt-Koyanagi-Harada disease. J Am Acad Dermatol 2001;44:129–31.
CrossRef
Google scholar
|
[16] |
Chi W, Yang P, Li B, et al. IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. J Allergy Clin Immunol 2007;119:1218–24.
CrossRef
Google scholar
|
[17] |
Ohta K, Yoshimura N. Bcl-2 expression by CD4 T lymphocytes in Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm 2002;10:93–103.
CrossRef
Google scholar
|
[18] |
Caspi RR, Silver PB, Luger D, et al. Mouse models of experimental autoimmune uveitis. Ophthalmic Res 2008;40:169–74.
CrossRef
Google scholar
|
[19] |
Hu Y, Hu Y, Xiao Y, et al. Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease. Proc Natl Acad Sci USA 2020;117:25712–21.
CrossRef
Google scholar
|
[20] |
Chan CC, Palestine AG, Nussenblatt RB, et al. Anti-retinal auto-antibodies in Vogt-Koyanagi-Harada syndrome, Behcet’s disease, and sympathetic ophthalmia. Ophthalmology 1985;92:1025–8.
CrossRef
Google scholar
|
[21] |
El-Asrar AMA, Berghmans N, Al-Obeidan SA, et al. Differential CXC and CX3C chemokine expression profiles in aqueous humor of patients with specific endogenous uveitic entities. Invest Ophthalmol Vis Sci 2018;59:2222–8.
CrossRef
Google scholar
|
[22] |
Abu El-Asrar AM, Berghmans N, Al-Obeidan SA, et al. Local cytokine expression profiling in patients with specific autoimmune uveitic entities. Ocul Immunol Inflamm 2020;28:453462.
CrossRef
Google scholar
|
[23] |
Stuart T, Satija R. Integrative single-cell analysis. Nat Rev Genet 2019;20:257–72.
CrossRef
Google scholar
|
[24] |
Yamada S, Nomura S. Review of single-cell RNA sequencing in the heart. Int J Mol Sci 2020;21:8345.
CrossRef
Google scholar
|
[25] |
Zhang Y, Wang D, Peng M, et al. Single-cell RNA sequencing in cancer research. J Exp Clin Cancer Res 2021;40:81.
CrossRef
Google scholar
|
[26] |
Han J, DePinho RA, Maitra A. Single-cell RNA sequencing in pancreatic cancer. Nat Rev Gastroenterol Hepatol 2021;18:451–2.
CrossRef
Google scholar
|
[27] |
Dutertre CA, Becht E, Irac SE, et al. Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells. Immunity 2019;51:573–589.e578.
CrossRef
Google scholar
|
[28] |
Harasymowicz NS, Rashidi N, Savadipour A, et al. Single-cell RNA sequencing reveals the induction of novel myeloid and myeloid-associated cell populations in visceral fat with long-term obesity. FASEB J 2021;35:e21417.
CrossRef
Google scholar
|
[29] |
Xie X, Shi Q, Wu P, et al. Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection. Nat Immunol 2020;21:1119–33.
CrossRef
Google scholar
|
[30] |
Wilk AJ, Rustagi A, Zhao NQ, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med 2020;26:1070–6.
CrossRef
Google scholar
|
[31] |
Zhang W, Yang B, Weng L, et al. Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia. Aging 2020;12:25337–55.
CrossRef
Google scholar
|
[32] |
Blair TA, Michelson AD, Frelinger AL, et al. Mass cytometry reveals distinct platelet subtypes in healthy subjects and novel alterations in surface glycoproteins in Glanzmann thrombasthenia. Sci Rep 2018;8:10300.
CrossRef
Google scholar
|
[33] |
Wang S, Xia P, Chen Y, et al. Natural killer-like B cells prime innate lymphocytes against microbial infection. Immunity 2016;45:131–44.
CrossRef
Google scholar
|
[34] |
Wang S, Xia P, Fan Z. Natural-killer-like B Cells function as a separate subset of innate B cells. Immunity 2017;47:201–2.
CrossRef
Google scholar
|
[35] |
Zhang Y, Kuang W, Li D, et al. Natural killer-like B cells secreting interleukin-18 induces a proinflammatory response in periodontitis. Front Immunol 2021;12:641562.
CrossRef
Google scholar
|
[36] |
Liu S, Yang L, Jia S, et al. Interleukin-35 suppresses the activity of natural killer-like B cells in patients with hepatocellular carcinoma. Int Immunopharmacol 2021;100:108161.
CrossRef
Google scholar
|
[37] |
Ahmed R, Omidian Z, Giwa A, et al. A public BCR present in a unique dual-receptor-expressing lymphocyte from Type 1 diabetes patients encodes a potent T cell autoantigen. Cell 2019;177:1583–1599.e16.
CrossRef
Google scholar
|
[38] |
Yang J, Sundrud MS, Skepner J, et al. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci 2014;35:493–500.
CrossRef
Google scholar
|
[39] |
Nicholson LB, Kuchroo VK. Manipulation of the Th1/Th2 balance in autoimmune disease. Curr Opin Immunol 1996;8:837–42.
CrossRef
Google scholar
|
[40] |
Zhou L, Ivanov II, Spolski R, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007;8:967–74.
CrossRef
Google scholar
|
[41] |
McGinley AM, Sutton CE, Edwards SC, et al. Interleukin-17A serves a priming role in autoimmunity by recruiting IL-1β-producing myeloid cells that promote pathogenic T cells. Immunity 2020;52:342–356.e6.
CrossRef
Google scholar
|
[42] |
Dinarello CA. IL-18: a TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 1999;103:11–24.
CrossRef
Google scholar
|
[43] |
Shevach EM, Chang JT, Segal BM. The critical role of IL-12 and the IL-12R beta 2 subunit in the generation of pathogenic autoreactive Th1 cells. Springer Semin Immunopathol 1999;21:249–62.
CrossRef
Google scholar
|
[44] |
Abbas AK, Trotta E, Simeonov DR, et al. Revisiting IL-2: biology and therapeutic prospects. Sci Immunol 2018;3:eaat1482.
CrossRef
Google scholar
|
[45] |
Picelli S. Single-cell RNA-sequencing: the future of genome biology is now. RNA Biol 2017;14:637–50.
CrossRef
Google scholar
|
[46] |
Silpa-Archa S, Silpa-Archa N, Preble JM, et al. Vogt-Koyanagi-Harada syndrome: perspectives for immunogenetics, multimodal imaging, and therapeutic options. Autoimmun Rev 2016;15:809–19.
CrossRef
Google scholar
|
[47] |
Greco A, Fusconi M, Gallo A, et al. Vogt-Koyanagi-Harada syndrome. Autoimmun Rev 2013;12:1033–8.
CrossRef
Google scholar
|
[48] |
Nicholson LB, Raveney BJ, Munder M. Monocyte dependent regulation of autoimmune inflammation. Curr Mol Med 2009;9:23–9.
CrossRef
Google scholar
|
[49] |
Flaherty S, Reynolds JM. Mouse naïve CD4+ T cell isolation and in vitro differentiation into T cell subsets. J Vis Exp JoVE 2015;(98):52739.
|
[50] |
Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015;15:486–99.
CrossRef
Google scholar
|
[51] |
Musette P, Bouaziz JD. B cell modulation strategies in autoimmune diseases: new concepts. Front Immunol 2018;9:622.
CrossRef
Google scholar
|
[52] |
Myhr KM, Torkildsen O, Lossius A, et al. B cell depletion in the treatment of multiple sclerosis. Expert Opin Biol Ther 2019;19:261–71.
CrossRef
Google scholar
|
[53] |
Guo L, Kapur R, Aslam R, et al. CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia. Blood 2016;127:735–8.
CrossRef
Google scholar
|
[54] |
Jagessar SA, Heijmans N, Bauer J, et al. B-cell depletion abrogates T cell-mediated demyelination in an antibody-nondependent common marmoset experimental autoimmune encephalomyelitis model. J Neuropathol Exp Neurol 2012;71:716–28.
CrossRef
Google scholar
|
[55] |
Zheng Y, Liu X, Le W, et al. A human circulating immune cell landscape in aging and COVID-19. Protein Cell 2020;11:740–70.
CrossRef
Google scholar
|
[56] |
Bing SJ, Shemesh I, Chong WP, et al. AS101 ameliorates experimental autoimmune uveitis by regulating Th1 and Th17 responses and inducing Treg cells. J Autoimmun 2019;100:52–61.
CrossRef
Google scholar
|
[57] |
Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. Semin Immunopathol 2019;41:283–97.
CrossRef
Google scholar
|
[58] |
Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10:1523.
CrossRef
Google scholar
|
[59] |
Chen TJ, Kotecha N. Cytobank: providing an analytics platform for community cytometry data analysis and collaboration. High-dimensional single cell analysis: Mass cytometry, multi-parametric flow cytometry and bioinformatic techniques 2014;127–157.
CrossRef
Google scholar
|
/
〈 | 〉 |