Journal article
Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells
The Journal of immunology (1950), Vol.202(5), pp.1441-1452
03/01/2019
DOI: 10.4049/jimmunol.1701204
PMCID: PMC6382580
PMID: 30692211
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
mice develop ameliorated experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, whereas
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.
Details
- Title: Subtitle
- Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells
- Creators
- Song Ouyang - Medical Center of Neurology, First Hospital of Changsha City, South China University, Changsha, Hunan 410005, People's Republic of ChinaQiuming Zeng - Department of Pathology, University of Iowa, Iowa City, IA 52242Na Tang - Hunan Normal UniversityHui Guo - University of Iowa, PathologyRong Tang - Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of ChinaWeifan Yin - Central South UniversityAimin Wang - Medical Center of Neurology, First Hospital of Changsha City, South China University, Changsha, Hunan 410005, People's Republic of ChinaHongyu Tang - Medical Center of Neurology, First Hospital of Changsha City, South China University, Changsha, Hunan 410005, People's Republic of ChinaJiru Zhou - Department of Cardiothoracic Surgery, First Hospital of Changsha City, South China University, Changsha, Hunan 410005, People's Republic of China; andHong Xie - Medical Center of Neurology, First Hospital of Changsha City, South China University, Changsha, Hunan 410005, People's Republic of ChinaWallace Y Langdon - The University of Western AustraliaHuan Yang - Xiangya Hospital Central South UniversityJian Zhang - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.202(5), pp.1441-1452
- DOI
- 10.4049/jimmunol.1701204
- PMID
- 30692211
- PMCID
- PMC6382580
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI121196 / NIAID NIH HHS R01 AI123253 / NIAID NIH HHS R01 AI090901 / NIAID NIH HHS R21 AI117547 / NIAID NIH HHS
- Language
- English
- Date published
- 03/01/2019
- Academic Unit
- Pathology
- Record Identifier
- 9984196358802771
Metrics
40 Record Views