Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells

Song Ouyang, Qiuming Zeng, Na Tang, Hui Guo, Rong Tang, Weifan Yin, Aimin Wang, Hongyu Tang, Jiru Zhou, Hong Xie, Wallace Y. Langdon, Huan Yang, Jian Zhang

Research output: Contribution to journalArticle

Abstract

Akt isoforms play key roles in multiple cellular processes; however, the roles of Akt-1 and Akt-2 isoforms in the development of T cell-mediated autoimmunity are poorly defined. In this study, we showed that Akt1(-/-) mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas Akt2(-/-) mice develop exacerbated EAE, compared with wild-type mice. At the cellular level, Akt-1 appears to inhibit proliferation of thymus-derived regulatory T cells (tTregs), which facilitates Ag-specific Th1/Th17 responses. In a sharp contrast to Akt-1, Akt-2 potentiates tTreg proliferation in vitro and in vivo and suppresses Ag-specific Th1/Th17 responses. Furthermore, treating mice with established EAE with a specific Akt-1 inhibitor suppressed disease progression. Our data demonstrate that Akt-1 and Akt-2 differentially regulate the susceptibility of mice to EAE by controlling tTreg proliferation. Our data also indicate that targeting Akt-1 is a potential therapeutic approach for multiple sclerosis in humans.

Original languageEnglish
Pages (from-to)1441-1452
Number of pages12
JournalJournal of Immunology
Volume202
Issue number5
DOIs
Publication statusPublished - 1 Mar 2019

Cite this

Ouyang, Song ; Zeng, Qiuming ; Tang, Na ; Guo, Hui ; Tang, Rong ; Yin, Weifan ; Wang, Aimin ; Tang, Hongyu ; Zhou, Jiru ; Xie, Hong ; Langdon, Wallace Y. ; Yang, Huan ; Zhang, Jian. / Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells. In: Journal of Immunology. 2019 ; Vol. 202, No. 5. pp. 1441-1452.
@article{1c9d4663807342138c0713b86457e257,
title = "Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells",
abstract = "Akt isoforms play key roles in multiple cellular processes; however, the roles of Akt-1 and Akt-2 isoforms in the development of T cell-mediated autoimmunity are poorly defined. In this study, we showed that Akt1(-/-) mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas Akt2(-/-) mice develop exacerbated EAE, compared with wild-type mice. At the cellular level, Akt-1 appears to inhibit proliferation of thymus-derived regulatory T cells (tTregs), which facilitates Ag-specific Th1/Th17 responses. In a sharp contrast to Akt-1, Akt-2 potentiates tTreg proliferation in vitro and in vivo and suppresses Ag-specific Th1/Th17 responses. Furthermore, treating mice with established EAE with a specific Akt-1 inhibitor suppressed disease progression. Our data demonstrate that Akt-1 and Akt-2 differentially regulate the susceptibility of mice to EAE by controlling tTreg proliferation. Our data also indicate that targeting Akt-1 is a potential therapeutic approach for multiple sclerosis in humans.",
keywords = "LIGASE CBL-B, MULTIPLE-SCLEROSIS PATIENTS, SUPPRESSIVE FUNCTION, FOXP3 EXPRESSION, ACTIVATION, DISEASE, PROTEIN, CNS, PROTECTION, RESPONSES",
author = "Song Ouyang and Qiuming Zeng and Na Tang and Hui Guo and Rong Tang and Weifan Yin and Aimin Wang and Hongyu Tang and Jiru Zhou and Hong Xie and Langdon, {Wallace Y.} and Huan Yang and Jian Zhang",
year = "2019",
month = "3",
day = "1",
doi = "10.4049/jimmunol.1701204",
language = "English",
volume = "202",
pages = "1441--1452",
journal = "The Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells. / Ouyang, Song; Zeng, Qiuming; Tang, Na; Guo, Hui; Tang, Rong; Yin, Weifan; Wang, Aimin; Tang, Hongyu; Zhou, Jiru; Xie, Hong; Langdon, Wallace Y.; Yang, Huan; Zhang, Jian.

In: Journal of Immunology, Vol. 202, No. 5, 01.03.2019, p. 1441-1452.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells

AU - Ouyang, Song

AU - Zeng, Qiuming

AU - Tang, Na

AU - Guo, Hui

AU - Tang, Rong

AU - Yin, Weifan

AU - Wang, Aimin

AU - Tang, Hongyu

AU - Zhou, Jiru

AU - Xie, Hong

AU - Langdon, Wallace Y.

AU - Yang, Huan

AU - Zhang, Jian

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Akt isoforms play key roles in multiple cellular processes; however, the roles of Akt-1 and Akt-2 isoforms in the development of T cell-mediated autoimmunity are poorly defined. In this study, we showed that Akt1(-/-) mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas Akt2(-/-) mice develop exacerbated EAE, compared with wild-type mice. At the cellular level, Akt-1 appears to inhibit proliferation of thymus-derived regulatory T cells (tTregs), which facilitates Ag-specific Th1/Th17 responses. In a sharp contrast to Akt-1, Akt-2 potentiates tTreg proliferation in vitro and in vivo and suppresses Ag-specific Th1/Th17 responses. Furthermore, treating mice with established EAE with a specific Akt-1 inhibitor suppressed disease progression. Our data demonstrate that Akt-1 and Akt-2 differentially regulate the susceptibility of mice to EAE by controlling tTreg proliferation. Our data also indicate that targeting Akt-1 is a potential therapeutic approach for multiple sclerosis in humans.

AB - Akt isoforms play key roles in multiple cellular processes; however, the roles of Akt-1 and Akt-2 isoforms in the development of T cell-mediated autoimmunity are poorly defined. In this study, we showed that Akt1(-/-) mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas Akt2(-/-) mice develop exacerbated EAE, compared with wild-type mice. At the cellular level, Akt-1 appears to inhibit proliferation of thymus-derived regulatory T cells (tTregs), which facilitates Ag-specific Th1/Th17 responses. In a sharp contrast to Akt-1, Akt-2 potentiates tTreg proliferation in vitro and in vivo and suppresses Ag-specific Th1/Th17 responses. Furthermore, treating mice with established EAE with a specific Akt-1 inhibitor suppressed disease progression. Our data demonstrate that Akt-1 and Akt-2 differentially regulate the susceptibility of mice to EAE by controlling tTreg proliferation. Our data also indicate that targeting Akt-1 is a potential therapeutic approach for multiple sclerosis in humans.

KW - LIGASE CBL-B

KW - MULTIPLE-SCLEROSIS PATIENTS

KW - SUPPRESSIVE FUNCTION

KW - FOXP3 EXPRESSION

KW - ACTIVATION

KW - DISEASE

KW - PROTEIN

KW - CNS

KW - PROTECTION

KW - RESPONSES

U2 - 10.4049/jimmunol.1701204

DO - 10.4049/jimmunol.1701204

M3 - Article

VL - 202

SP - 1441

EP - 1452

JO - The Journal of Immunology

JF - The Journal of Immunology

SN - 0022-1767

IS - 5

ER -