Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline

Luming Zhou; Guiping Kong; Ilaria Palmisano; Maria Teresa Cencioni; Matt Danzi; Francesco De Virgiliis; Jessica S Chadwick; Greg Crawford; Zicheng Yu; Fred De Winter; Vance Lemmon; John Bixby; Radhika Puttagunta; Joost Verhaagen; Constandina Pospori; Cristina Lo Celso; Jessica Strid; Marina Botto; Simone Di Giovanni

doi:10.1126/science.abd5926

Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline

Luming Zhou, Guiping Kong, Ilaria Palmisano, Maria Teresa Cencioni, Matt Danzi, Francesco De Virgiliis, Jessica S Chadwick, Greg Crawford, Zicheng Yu, Fred De Winter, Vance Lemmon, John Bixby, Radhika Puttagunta, Joost Verhaagen, Constandina Pospori, Cristina Lo Celso, Jessica Strid, Marina Botto, Simone Di Giovanni

NIN

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

49 Citaten (Scopus)

Samenvatting

Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5+CD8+ T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8+ T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5+CD8+ T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.

Originele taal-2	Engels
Pagina's (van-tot)	eabd5926
Tijdschrift	Science
Volume	376
Nummer van het tijdschrift	6594
DOI's	https://doi.org/10.1126/science.abd5926
Status	Gepubliceerd - 13 mei 2022

Toegang tot document

10.1126/science.abd5926

Citeer dit

Zhou, L., Kong, G., Palmisano, I., Cencioni, M. T., Danzi, M., De Virgiliis, F., Chadwick, J. S., Crawford, G., Yu, Z., De Winter, F., Lemmon, V., Bixby, J., Puttagunta, R., Verhaagen, J., Pospori, C., Lo Celso, C., Strid, J., Botto, M., & Di Giovanni, S. (2022). Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline. Science, 376(6594), eabd5926. https://doi.org/10.1126/science.abd5926

@article{ea78870cbd094147b04f5f40734486e1,

title = "Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline",

abstract = "Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5+CD8+ T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8+ T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5+CD8+ T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.",

author = "Luming Zhou and Guiping Kong and Ilaria Palmisano and Cencioni, {Maria Teresa} and Matt Danzi and {De Virgiliis}, Francesco and Chadwick, {Jessica S} and Greg Crawford and Zicheng Yu and {De Winter}, Fred and Vance Lemmon and John Bixby and Radhika Puttagunta and Joost Verhaagen and Constandina Pospori and {Lo Celso}, Cristina and Jessica Strid and Marina Botto and {Di Giovanni}, Simone",

year = "2022",

month = may,

day = "13",

doi = "10.1126/science.abd5926",

language = "English",

volume = "376",

pages = "eabd5926",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "6594",

}

Zhou, L, Kong, G, Palmisano, I, Cencioni, MT, Danzi, M, De Virgiliis, F, Chadwick, JS, Crawford, G, Yu, Z, De Winter, F, Lemmon, V, Bixby, J, Puttagunta, R, Verhaagen, J, Pospori, C, Lo Celso, C, Strid, J, Botto, M & Di Giovanni, S 2022, 'Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline', Science, vol. 376, nr. 6594, blz. eabd5926. https://doi.org/10.1126/science.abd5926

TY - JOUR

T1 - Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline

AU - Zhou, Luming

AU - Kong, Guiping

AU - Palmisano, Ilaria

AU - Cencioni, Maria Teresa

AU - Danzi, Matt

AU - De Virgiliis, Francesco

AU - Chadwick, Jessica S

AU - Crawford, Greg

AU - Yu, Zicheng

AU - De Winter, Fred

AU - Lemmon, Vance

AU - Bixby, John

AU - Puttagunta, Radhika

AU - Verhaagen, Joost

AU - Pospori, Constandina

AU - Lo Celso, Cristina

AU - Strid, Jessica

AU - Botto, Marina

AU - Di Giovanni, Simone

PY - 2022/5/13

Y1 - 2022/5/13

N2 - Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5+CD8+ T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8+ T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5+CD8+ T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.

AB - Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5+CD8+ T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8+ T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5+CD8+ T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.

U2 - 10.1126/science.abd5926

DO - 10.1126/science.abd5926

M3 - Article

C2 - 35549409

SN - 0036-8075

VL - 376

SP - eabd5926

JO - Science

JF - Science

IS - 6594

ER -

Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline

Samenvatting

Toegang tot document

Vingerafdruk

Citeer dit