A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity

Karina Pino-Lagos; Yanxia Guo; Chrysothemis Brown; Matthew P. Alexander; Raúl Elgueta; Kathryn A. Bennett; Victor De Vries; Elizabeth Nowak; Rune Blomhoff; Shanthini Sockanathan; Roshantha A. Chandraratna; Ethan Dmitrovsky; Randolph J. Noelle

doi:10.1084/jem.20102358

A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity

Karina Pino-Lagos, Yanxia Guo, Chrysothemis Brown, Matthew P. Alexander, Raúl Elgueta, Kathryn A. Bennett, Victor De Vries, Elizabeth Nowak, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Randolph J. Noelle

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Abstract

It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4(+) T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4(+) T cell differentiation and immunity.

Original language	English
Pages (from-to)	1767-1775
Number of pages	9
Journal	Journal of Experimental Medicine
Volume	208
Issue number	9
DOIs	https://doi.org/10.1084/jem.20102358
Publication status	Published - 29 Aug 2011

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A retinoic acid–dependent checkpoint in the development of CD4+ T cell–mediated immunity GreenPDFFinal published version, 1.93 MBLicence: CC BY-NC-SA

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Pino-Lagos, K., Guo, Y., Brown, C., Alexander, M. P., Elgueta, R., Bennett, K. A., De Vries, V., Nowak, E., Blomhoff, R., Sockanathan, S., Chandraratna, R. A., Dmitrovsky, E., & Noelle, R. J. (2011). A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity. Journal of Experimental Medicine, 208(9), 1767-1775. https://doi.org/10.1084/jem.20102358

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title = "A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity",

abstract = "It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4(+) T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4(+) T cell differentiation and immunity.",

author = "Karina Pino-Lagos and Yanxia Guo and Chrysothemis Brown and Alexander, {Matthew P.} and Ra{\'u}l Elgueta and Bennett, {Kathryn A.} and {De Vries}, Victor and Elizabeth Nowak and Rune Blomhoff and Shanthini Sockanathan and Chandraratna, {Roshantha A.} and Ethan Dmitrovsky and Noelle, {Randolph J.}",

year = "2011",

month = aug,

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doi = "10.1084/jem.20102358",

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journal = "Journal of Experimental Medicine",

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Pino-Lagos, K, Guo, Y, Brown, C, Alexander, MP, Elgueta, R, Bennett, KA, De Vries, V, Nowak, E, Blomhoff, R, Sockanathan, S, Chandraratna, RA, Dmitrovsky, E & Noelle, RJ 2011, 'A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity', Journal of Experimental Medicine, vol. 208, no. 9, pp. 1767-1775. https://doi.org/10.1084/jem.20102358

TY - JOUR

T1 - A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity

AU - Pino-Lagos, Karina

AU - Guo, Yanxia

AU - Brown, Chrysothemis

AU - Alexander, Matthew P.

AU - Elgueta, Raúl

AU - Bennett, Kathryn A.

AU - De Vries, Victor

AU - Nowak, Elizabeth

AU - Blomhoff, Rune

AU - Sockanathan, Shanthini

AU - Chandraratna, Roshantha A.

AU - Dmitrovsky, Ethan

AU - Noelle, Randolph J.

PY - 2011/8/29

Y1 - 2011/8/29

N2 - It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4(+) T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4(+) T cell differentiation and immunity.

AB - It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4(+) T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4(+) T cell differentiation and immunity.

U2 - 10.1084/jem.20102358

DO - 10.1084/jem.20102358

M3 - Article

C2 - 21859847

VL - 208

SP - 1767

EP - 1775

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 9

ER -

A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity

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