Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry

被引：1028

作者：

Zhang, Fan ^{[1
,2
,3
,4
,5
,6
]}

Wei, Kevin ^{[3
,6
]}

Slowikowski, Kamil ^{[1
,2
,3
,4
,5
,6
]}

Fonseka, Chamith Y. ^{[1
,2
,3
,4
,5
,6
]}

Rao, Deepak A. ^{[3
,6
]}

Kelly, Stephen ^{[7
]}

Goodman, Susan M. ^{[8
,9
]}

Tabechian, Darren ^{[10
]}

Hughes, Laura B. ^{[11
]}

Salomon-Escoto, Karen ^{[12
]}

Watts, Gerald F. M. ^{[3
,6
]}

Jonsson, A. Helena ^{[3
,6
]}

Rangel-Moreno, Javier ^{[10
]}

Meednu, Nida ^{[10
]}

Rozo, Cristina ^{[13
]}

Apruzzese, William ^{[3
,6
]}

Eisenhaure, Thomas M. ^{[5
]}

Lieb, David J. ^{[5
]}

Boyle, David L. ^{[14
]}

Mandelin, Arthur M., II ^{[15
]}

Boyce, Brendan F.

DiCarlo, Edward ^{[16
]}

Gravallese, Ellen M. ^{[12
]}

Gregersen, Peter K. ^{[17
]}

Moreland, Larry ^{[18
]}

Firestein, Gary S. ^{[14
]}

Hacohen, Nir ^{[5
]}

Nusbaum, Chad ^{[5
]}

Lederer, James A. ^{[3
,19
]}

Perlman, Harris ^{[15
]}

Pitzalis, Costantino ^{[20
]}

Filer, Andrew ^{[21
,22
,23
]}

Holers, V. Michael ^{[24
]}

Bykerk, Vivian P. ^{[8
,9
]}

Donlin, Laura T. ^{[9
,13
]}

Anolik, Jennifer H. ^{[10
,25
]}

Brenner, Michael B. ^{[3
,6
]}

Raychaudhuri, Soumya ^{[1
,2
,3
,4
,5
,6
,26
]}

Albrecht, Jennifer ^{[10
]}

Bridges, S. Louis, Jr. ^{[11
]}

Buckley, Christopher D. ^{[21
,22
]}

Buckner, Jane H. ^{[27
]}

Dolan, James ^{[3
,19
]}

Guthridge, Joel M. ^{[28
]}

Gutierrez-Arcelus, Maria ^{[1
,2
,3
,4
,5
,6
]}

Ivashkiv, Lionel B. ^{[9
,29
,30
]}

James, Eddie A. ^{[27
]}

James, Judith A. ^{[28
]}

Keegan, Josh ^{[3
,19
]}

Lee, Yvonne C. ^{[15
]}

机构：

[1] Brigham & Womens Hosp, Ctr Data Sci, 75 Francis St, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[5] Broad Inst & Harvard, Cambridge, MA 02142 USA

[6] Brigham & Womens Hosp, Div Rheumatol, Immunol, Allergy, 75 Francis St, Boston, MA 02115 USA

[7] Barts Hlth NHS Trust, Dept Rheumatol, London, England

[8] Hosp Special Surg, Div Rheumatol, 535 E 70th St, New York, NY 10021 USA

[9] Weill Cornell Med Coll, Dept Med, New York, NY USA

[10] Univ Rochester, Med Ctr, Dept Med, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA

[11] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA

[12] Univ Massachusetts, Sch Med, Dept Med, Div Rheumatol, Worcester, MA USA

[13] Hosp Special Surg, Arthrit & Tissue Degenerat, 535 E 70th St, New York, NY 10021 USA

[14] Univ Calif San Diego, Dept Med, Div Rheumatol Allergy & Immunol, La Jolla, CA 92093 USA

[15] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA

[16] Hosp Special Surg, Dept Pathol & Lab Med, 535 E 70th St, New York, NY 10021 USA

[17] Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA

[18] Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA

[19] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA

[20] Queen Mary Univ London, William Harvey Res Inst, Ctr Expt Med & Rheumatol, London, England

[21] Univ Hosp Birmingham NHS Fdn Trust, NIHR Birmingham Biomed Res Ctr, Birmingham, W Midlands, England

[22] Univ Birmingham, Birmingham, W Midlands, England

[23] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England

[24] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA

[25] Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Rochester, NY 14642 USA

[26] Univ Manchester, Ctr Musculoskeletal Res, Arthrit Res UK Ctr Genet & Gen, Manchester, Lancs, England

[27] Virginia Mason, Benaroya Res Inst, Translat Res Program, Seattle, VA USA

[28] Oklahoma Med Res Fdn, Dept Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA

[29] Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenes, New York, NY USA

[30] Hosp Special Surg, David Z Rosensweig Genom Res Ctr, 535 E 70th St, New York, NY 10021 USA

[31] Tokyo Med & Dent Univ, Dept Rheumatol, Grad Sch Med & Dent Sci, Tokyo, Japan

[32] Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA

[33] Stanford Univ, Sch Med, Dept Med, Div Immunol & Rheumatol, Palo Alto, CA 94304 USA

[34] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 07期

基金：

美国国家卫生研究院; 英国惠康基金; 新加坡国家研究基金会;

关键词：

B-CELLS; SUBSETS; PATHOPHYSIOLOGY; PATHOGENESIS; FIBROBLASTS; MACROPHAGES; EXPRESSION; SYSTEM; IMMUNE;

D O I：

10.1038/s41590-019-0378-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to Tcells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)(+)HLA-DRA(hi) sublining fibroblasts, IL1B(+) pro-inflammatory monocytes, ITGAX(+)TBX21(+) autoimmune-associated B cells and PDCD1(+) peripheral helper T (T-PH) cells and follicular helper T (T-FH) cells. We defined distinct subsets of CD8(+)Tcells characterized by GZMIK(+), GZMB(+), and GNLY(+) phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed 1L6 expression to THYl(+)HLA-DRA(hi) fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

引用

页码：928 / +

页数：18

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