Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

Emanuela Pasciuto; Oliver T Burton; Carlos P Roca; Vasiliki Lagou; Wenson D Rajan; Tom Theys; Renzo Mancuso; Raul Y Tito; Lubna Kouser; Zsuzsanna Callaerts-Vegh; Alerie G de la Fuente; Teresa Prezzemolo; Loriana G Mascali; Aleksandra Brajic; Carly E Whyte; Lidia Yshii; Anna Martinez-Muriana; Michelle Naughton; Andrew Young; Alena Moudra; Pierre Lemaitre; Suresh Poovathingal; Jeroen Raes; Bart De Strooper; Denise C Fitzgerald; James Dooley; Adrian Liston

doi:10.1016/j.cell.2020.06.026

Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

Emanuela Pasciuto, Oliver T Burton, Carlos P Roca, Vasiliki Lagou, Wenson D Rajan, Tom Theys, Renzo Mancuso, Raul Y Tito, Lubna Kouser, Zsuzsanna Callaerts-Vegh, Alerie G de la Fuente, Teresa Prezzemolo, Loriana G Mascali, Aleksandra Brajic, Carly E Whyte, Lidia Yshii, Anna Martinez-Muriana, Michelle Naughton, Andrew Young, Alena MoudraPierre Lemaitre, Suresh Poovathingal, Jeroen Raes, Bart De Strooper, Denise C Fitzgerald, James Dooley, Adrian Liston

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Abstract

The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.

Original language	English
Pages (from-to)	625
Journal	Cell
Volume	182
Issue number	3
Early online date	20 Jul 2020
DOIs	https://doi.org/10.1016/j.cell.2020.06.026
Publication status	Early online date - 20 Jul 2020

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Microglia Require CD4 T Cells to Complete the Fetalto-Adult Transition
© 2020 The Authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 11.8 MBLicence: CC BY-NC-ND

Denise Fitzgerald
- d.fitzgeraldqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Professor
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic

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Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., de la Fuente, A. G., Prezzemolo, T., Mascali, L. G., Brajic, A., Whyte, C. E., Yshii, L., Martinez-Muriana, A., Naughton, M., Young, A., ... Liston, A. (2020). Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition. Cell, 182(3), 625. Advance online publication. https://doi.org/10.1016/j.cell.2020.06.026

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title = "Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition",

abstract = "The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.",

author = "Emanuela Pasciuto and Burton, {Oliver T} and Roca, {Carlos P} and Vasiliki Lagou and Rajan, {Wenson D} and Tom Theys and Renzo Mancuso and Tito, {Raul Y} and Lubna Kouser and Zsuzsanna Callaerts-Vegh and {de la Fuente}, {Alerie G} and Teresa Prezzemolo and Mascali, {Loriana G} and Aleksandra Brajic and Whyte, {Carly E} and Lidia Yshii and Anna Martinez-Muriana and Michelle Naughton and Andrew Young and Alena Moudra and Pierre Lemaitre and Suresh Poovathingal and Jeroen Raes and {De Strooper}, Bart and Fitzgerald, {Denise C} and James Dooley and Adrian Liston",

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Pasciuto, E, Burton, OT, Roca, CP, Lagou, V, Rajan, WD, Theys, T, Mancuso, R, Tito, RY, Kouser, L, Callaerts-Vegh, Z, de la Fuente, AG, Prezzemolo, T, Mascali, LG, Brajic, A, Whyte, CE, Yshii, L, Martinez-Muriana, A, Naughton, M , Young, A, Moudra, A, Lemaitre, P, Poovathingal, S, Raes, J, De Strooper, B, Fitzgerald, DC, Dooley, J & Liston, A 2020, 'Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition', Cell, vol. 182, no. 3, pp. 625. https://doi.org/10.1016/j.cell.2020.06.026

TY - JOUR

T1 - Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

AU - Pasciuto, Emanuela

AU - Burton, Oliver T

AU - Roca, Carlos P

AU - Lagou, Vasiliki

AU - Rajan, Wenson D

AU - Theys, Tom

AU - Mancuso, Renzo

AU - Tito, Raul Y

AU - Kouser, Lubna

AU - Callaerts-Vegh, Zsuzsanna

AU - de la Fuente, Alerie G

AU - Prezzemolo, Teresa

AU - Mascali, Loriana G

AU - Brajic, Aleksandra

AU - Whyte, Carly E

AU - Yshii, Lidia

AU - Martinez-Muriana, Anna

AU - Naughton, Michelle

AU - Young, Andrew

AU - Moudra, Alena

AU - Lemaitre, Pierre

AU - Poovathingal, Suresh

AU - Raes, Jeroen

AU - De Strooper, Bart

AU - Fitzgerald, Denise C

AU - Dooley, James

AU - Liston, Adrian

PY - 2020/7/20

Y1 - 2020/7/20

N2 - The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.

AB - The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.

U2 - 10.1016/j.cell.2020.06.026

DO - 10.1016/j.cell.2020.06.026

M3 - Article

C2 - 32702313

SN - 0092-8674

VL - 182

SP - 625

JO - Cell

JF - Cell

IS - 3

ER -

Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

Abstract

Bibliographical note

UN SDGs

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Denise Fitzgerald

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