The immune cell landscape in kidneys of patients with lupus nephritis

被引：573

作者：

Arazi, Arnon ^{[1
,2
]}

Rao, Deepak A. ^{[2
]}

Berthier, Celine C. ^{[3
]}

Davidson, Anne ^{[4
]}

Liu, Yanyan ^{[2
]}

Hoover, Paul J. ^{[1
]}

Chicoine, Adam ^{[2
]}

Eisenhaure, Thomas M. ^{[1
]}

Jonsson, A. Helena ^{[2
]}

Li, Shuqiang ^{[1
]}

Lieb, David J. ^{[1
]}

Zhang, Fan ^{[2
]}

Slowikowski, Kamil ^{[2
]}

Browne, Edward P. ^{[5
,6
]}

Noma, Akiko ^{[1
]}

Sutherby, Danielle ^{[7
]}

Steelman, Scott ^{[8
]}

Smilek, Dawn E. ^{[9
,10
]}

Tosta, Patti ^{[9
,10
]}

Apruzzese, William ^{[2
]}

Massarotti, Elena ^{[2
]}

Dall'Era, Maria ^{[11
]}

Park, Meyeon ^{[12
]}

Kamen, Diane L. ^{[13
]}

Furie, Richard A. ^{[14
]}

Payan-Schober, Fernanda ^{[15
]}

Pendergraft, William F., III ^{[16
]}

McInnis, Elizabeth A. ^{[17
]}

Buyon, Jill P. ^{[18
]}

Petri, Michelle A. ^{[19
]}

Putterman, Chaim ^{[20
,21
,22
]}

Kalunian, Kenneth C. ^{[23
]}

Woodle, E. Steve ^{[24
]}

Lederer, James A. ^{[25
]}

Hildeman, David A. ^{[26
,27
]}

Nusbaum, Chad ^{[8
]}

Raychaudhuri, Soumya ^{[2
]}

Kretzler, Matthias ^{[3
]}

Anolik, Jennifer H. ^{[28
]}

Brenner, Michael B. ^{[2
]}

Wofsy, David ^{[11
]}

Hacohen, Nir ^{[1
]}

Diamond, Betty ^{[4
]}

Waguespack, Dia ^{[29
]}

Connery, Sean M. ^{[15
]}

McMahon, Maureen A. ^{[30
]}

McCune, William J. ^{[3
]}

Kado, Ruba B. ^{[3
]}

Hsu, Raymond ^{[12
]}

Cunningham, Melissa A. ^{[13
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Rheumatol,Immunol,Allergy, Boston, MA 02115 USA

[3] Univ Michigan, Dept Nephrol, Internal Med, Ann Arbor, MI 48109 USA

[4] Northwell Hlth, Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA

[5] Univ N Carolina, UNC HIV Cure Ctr, Chapel Hill, NC USA

[6] Univ N Carolina, Dept Med, Chapel Hill, NC USA

[7] Celsius Therapeut, Cambridge, MA USA

[8] Cellarity Inc, Cambridge, MA USA

[9] Univ Calif San Francisco, Lupus Nephritis Trials Network, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, Immune Tolerance Network, San Francisco, CA 94143 USA

[11] Univ Calif San Francisco, Rheumatol Div, San Francisco, CA 94143 USA

[12] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA

[13] Med Univ South Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA

[14] Northwell Hlth, Div Rheumatol, Great Neck, NY USA

[15] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Med, El Paso, TX USA

[16] PLLC, Integrat Med Clin North Carolina, Chapel Hill, NC USA

[17] UNC, Sch Med, Dept Med, Kidney Ctr,Div Nephrol & Hypertens, Chapel Hill, NC USA

[18] NYU, Sch Med, Dept Med, Div Rheumatol, New York, NY USA

[19] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA

[20] Albert Einstein Coll Med, Div Rheumatol, Bronx, NY 10467 USA

[21] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA

[22] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA

[23] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA

[24] Univ Cincinnati, Coll Med, Dept Surg, Div Transplantat, Cincinnati, OH USA

[25] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

[26] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA

[27] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA

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

[29] Univ Texas Houston, Dept Internal Med, Houston, TX USA

[30] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[31] Stanford Univ, Dept Med, Sch Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA

[32] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

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

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

[35] Rockefeller Univ, Lab RNA Mol Biol, 1230 York Ave, New York, NY 10021 USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 07期

基金：

美国国家卫生研究院;

关键词：

STAGE RENAL-DISEASE; SELF-RENEWAL; B-CELL; EXPRESSION; AUTOIMMUNITY; EXHAUSTION; PHENOTYPE; GATEWAYS; C1Q;

D O I：

10.1038/s41590-019-0398-x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, Tcells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.

引用

页码：902 / +

页数：15

共 58 条

[1] Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation [J].

Adamson, Samantha E. ;

Griffiths, Rachael ;

Moravec, Radim ;

Senthivinayagam, Subramanian ;

Montgomery, Garren ;

Chen, Wenshu ;

Han, Jenny ;

Sharma, Poonam R. ;

Mullins, Garrett R. ;

Gorski, Stacey A. ;

Cooper, Jonathan A. ;

Kadl, Alexandra ;

Enfield, Kyle ;

Braciale, Thomas J. ;

Harris, Thurl E. ;

Leitinger, Norbert .

JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (04) :1311-1322

[2] Transcriptome analysis reveals similarities between human blood CD3- CD56bright cells and mouse CD127+ innate lymphoid cells [J].

Allan, David S. J. ;

Cerdeira, Ana Sofia ;

Ranjan, Anuisa ;

Kirkham, Christina L. ;

Aguilar, Oscar A. ;

Tanaka, Miho ;

Childs, Richard W. ;

Dunbar, Cynthia E. ;

Strominger, Jack L. ;

Kopcow, Hernan D. ;

Carlyle, James R. .

SCIENTIFIC REPORTS, 2017, 7

[3] destiny: diffusion maps for large-scale single cell data in R [J].

Angerer, Philipp ;

Haghverdi, Laleh ;

Buettner, Maren ;

Theis, Fabian J. ;

Marr, Carsten ;

Buettner, Florian .

BIOINFORMATICS, 2016, 32 (08) :1241-1243

[4] Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior [J].

Auffray, Cedric ;

Fogg, Darin ;

Garfa, Meriem ;

Elain, Gaelle ;

Join-Lambert, Olivier ;

Kayal, Samer ;

Sarnacki, Sabine ;

Cumano, Ana ;

Lauvau, Gregoire ;

Geissmann, Frederic .

SCIENCE, 2007, 317 (5838) :666-670

[5] Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients [J].

Banchereau, Romain ;

Hong, Seunghee ;

Cantarel, Brandi ;

Baldwin, Nicole ;

Baisch, Jeanine ;

Edens, Michelle ;

Cepika, Alma-Martina ;

Acs, Peter ;

Turner, Jacob ;

Anguiano, Esperanza ;

Vinod, Parvathi ;

Kahn, Shaheen ;

Obermoser, Gerlinde ;

Blankenship, Derek ;

Wakeland, Edward ;

Nassi, Lorien ;

Gotte, Alisa ;

Punaro, Marilynn ;

Liu, Yong-Jun ;

Banchereau, Jacques ;

Rossello-Urgell, Jose ;

Wright, Tracey ;

Pascual, Virginia .

CELL, 2016, 165 (03) :551-565

[6] Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression patterns [J].

Bengsch, Bertram ;

Ohtani, Takuya ;

Herati, Ramin Sedaghat ;

Bovenschen, Niels ;

Chang, Kyong-Mi ;

Wherry, E. John .

JOURNAL OF IMMUNOLOGICAL METHODS, 2018, 453 :3-10

[7] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[8] ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells [J].

Boddupalli, Chandra Sekhar ;

Nair, Shiny ;

Gray, Simon M. ;

Nowyhed, Heba N. ;

Verma, Rakesh ;

Gibson, Joanna A. ;

Abraham, Clara ;

Narayan, Deepak ;

Vasquez, Juan ;

Hedrick, Catherine C. ;

Flavell, Richard A. ;

Dhodapkar, Kavita M. ;

Kaech, Susan M. ;

Dhodapkar, Madhav V. .

JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (10) :3905-3916

[9] Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection [J].

Botta, Davide ;

Fuller, Michael J. ;

Marquez-Lago, Tatiana T. ;

Bachus, Holly ;

Bradley, John E. ;

Weinmann, Amy S. ;

Zajac, Allan J. ;

Randall, Troy D. ;

Lund, Frances E. ;

Leon, Beatriz ;

Ballesteros-Tato, Andre .

NATURE IMMUNOLOGY, 2017, 18 (11) :1249-+

[10] Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood [J].

Bratke, K ;

Kuepper, M ;

Bade, B ;

Virchow, JC ;

Luttmann, W .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (09) :2608-2616

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