Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis

被引：37

作者：

Kiss, Mate G. ^{[1
,2
,3
,4
,5
,6
,7
]}

Mindur, John E. ^{[5
,6
,7
]}

Yates, Abi G. ^{[1
,2
,3
,4
]}

Lee, Donghoon ^{[3
,4
,8
,9
,10
]}

Fullard, John F. ^{[3
,4
,8
,9
,10
]}

Anzai, Atsushi ^{[5
,6
,7
]}

Poller, Wolfram C. ^{[1
,2
,5
,6
,7
]}

Christie, Kathleen A. ^{[11
,12
]}

Iwamoto, Yoshiko ^{[5
,6
,7
]}

Roudko, Vladimir ^{[13
]}

Downey, Jeffrey ^{[1
,2
,5
,6
,7
]}

Chan, Christopher T. ^{[5
,6
,7
]}

Huynh, Pacific ^{[1
,2
,3
,4
]}

Janssen, Henrike ^{[1
,2
,5
,6
,7
]}

Ntranos, Achilles ^{[14
]}

Hoffmann, Jan D. ^{[1
,2
,3
,4
]}

Jacob, Walter ^{[1
,2
,3
,4
]}

Goswami, Sukanya ^{[1
,2
,3
,4
]}

Singh, Sumnima ^{[1
,2
,5
,6
,7
]}

Leppert, David

Kuhle, Jens ^{[15
,16
]}

Kim-Schulze, Seunghee ^{[13
]}

Nahrendorf, Matthias ^{[5
,6
,7
]}

Kleinstiver, Benjamin P. ^{[11
,12
]}

Probert, Fay ^{[1
,17
]}

Roussos, Panos ^{[4
,18
,19
]}

Swirski, Filip K. ^{[1
,2
,6
,7
,20
,21
]}

McAlpine, Cameron S. ^{[1
,2
,3
,4
,5
,6
,7
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Med Cardiol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Cardiovasc Res Inst, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[5] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA

[6] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

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

[8] Icahn Sch Med Mt Sinai, Dept Psychiat & Genet & Genom Sci, New York, NY USA

[9] Icahn Sch Med Mt Sinai, Ctr Dis Neurogenom, New York, NY USA

[10] Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY USA

[11] Massachusetts Gen Hosp, Ctr Genom Med, Dept Pathol, Boston, MA USA

[12] Harvard Med Sch, Dept Pathol, Boston, MA USA

[13] Icahn Sch Med Mt Sinai, Human Immune Monitoring Ctr, New York, NY USA

[14] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA

[15] Univ Basel, Univ Hosp Basel, Dept Med Clin Res & Biomed, Basel, Switzerland

[16] Univ Oxford, Dept Pharmacol, Oxford, England

[17] Univ Oxford, Dept Chem, Oxford, England

[18] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, New York, NY USA

[19] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY USA

[20] Icahn Sch Med Mt Sinai, Marc & Jennifer Lipschultz Precis Immunol Inst, New York, NY USA

[21] Icahn Sch Med Mt Sinai, Biomed Engn & Imaging Inst, New York, NY USA

来源：

IMMUNITY | 2023年 / 56卷 / 07期

基金：

奥地利科学基金会; 美国国家卫生研究院;

关键词：

COLONY-STIMULATING FACTOR; SEQUENTIAL INTERLEUKIN-3; TRANSGENIC MICE; GM-CSF; TARGET; EXPRESSION; BRAIN; IL-3; CELL;

D O I：

10.1016/j.immuni.2023.04.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44hiCD4+ T cells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-alpha (IL3Ralpha). Astrocytic and T cell IL-3 elicited an immune migratory and chemotactic program by IL-3Ralpha+ myeloid cells that enhanced CNS immune cell infiltration, exacerbating MS and its preclinical model. Multiregional snRNA-seq of human CNS tissue revealed the appearance of IL3RA-expressing myeloid cells with chemotactic programming in MS plaques. IL3RA expression by plaque myeloid cells and IL-3 amount in the cerebrospinal fluid predicted myeloid and T cell abundance in the CNS and correlated with MS severity. Our findings establish IL-3:IL-3RA as a glial-peripheral immune network that prompts immune cell recruitment to the CNS and worsens MS.

引用

页码：1502 / +

页数：22

共 46 条

[1] Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis [J].

Anzai, Atsushi ;

Mindur, John E. ;

Halle, Lennard ;

Sano, Soichi ;

Choi, Jennifer L. ;

He, Shun ;

McAlpine, Cameron S. ;

Chan, Christopher T. ;

Kahles, Florian ;

Valet, Colin ;

Fenn, Ashley M. ;

Nairz, Manfred ;

Rattik, Sara ;

Iwamoto, Yoshiko ;

Fairweather, DeLisa ;

Walsh, Kenneth ;

Libby, Peter ;

Nahrendorf, Matthias ;

Swirski, Filip K. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2019, 216 (02) :369-383

[2] Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases [J].

Bae, Sangsu ;

Park, Jeongbin ;

Kim, Jin-Soo .

BIOINFORMATICS, 2014, 30 (10) :1473-1475

[3] Multiple Sclerosis: Mechanisms and Immunotherapy [J].

Baecher-Allan, Clare ;

Kaskow, Belinda J. ;

Weiner, Howard L. .

NEURON, 2018, 97 (04) :742-768

[4] Comparative effects of three cytokine regimens after high-dose cyclophosphamide: Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF [J].

Ballestrero, A ;

Ferrando, F ;

Garuti, A ;

Basta, P ;

Gonella, R ;

Stura, P ;

Mela, GS ;

Sessarego, M ;

Gobbi, M ;

Patrone, F .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1296-1303

[5] Corticosteroid receptor expression and in vivo glucocorticoid sensitivity in multiple sclerosis [J].

Bechmann, L. ;

Busse, K. ;

Stoppe, M. ;

Cotte, S. ;

Ettrich, B. ;

Bergh, F. Then .

JOURNAL OF NEUROIMMUNOLOGY, 2014, 276 (1-2) :159-165

[6] Differential induction of interleukin-1β and tumour necrosis factor-α may account for specific patterns of leukocyte recruitment in the brain [J].

Blond, D ;

Campbell, SJ ;

Butchart, AG ;

Perry, VH ;

Anthony, DC .

BRAIN RESEARCH, 2002, 958 (01) :89-99

[7] Diversity of innate immune cell subsets across spatial and temporal scales in an EAE mouse model [J].

Caravagna, Celine ;

Jaouen, Alexandre ;

Desplat-Jego, Sophie ;

Fenrich, Keith K. ;

Bergot, Elise ;

Luche, Herve ;

Grenot, Pierre ;

Rougon, Genevieve ;

Malissen, Marie ;

Debarbieux, Franck .

SCIENTIFIC REPORTS, 2018, 8

[8] Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons [J].

Chavany, C ;

Vicario-Abejón, C ;

Miller, G ;

Jendoubi, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) :11354-11359

[9] Macrophage microglial-mediated primary demyelination and motor disease induced by the central nervous system production of interleukin-3 in transgenic mice [J].

Chiang, CS ;

Powell, HC ;

Gold, LH ;

Samimi, A ;

Campbell, IL .

JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (06) :1512-1524

[10] Identification of astrocyte regulators by nucleic acid cytometry [J].

Clark, Iain C. C. ;

Wheeler, Michael A. A. ;

Lee, Hong-Gyun ;

Li, Zhaorong ;

Sanmarco, Liliana M. M. ;

Thaploo, Shravan ;

Polonio, Carolina M. M. ;

Shin, Seung Won ;

Scalisi, Giulia ;

Henry, Amy R. R. ;

Rone, Joseph M. M. ;

Giovannoni, Federico ;

Charabati, Marc ;

Akl, Camilo Faust ;

Aleman, Dulce M. M. ;

Zandee, Stephanie E. J. ;

Prat, Alexandre ;

Douek, Daniel C. C. ;

Boritz, Eli A. A. ;

Quintana, Francisco J. J. ;

Abate, Adam R. R. .

NATURE, 2023, 614 (7947) :326-+

← 1 2 3 4 5 →