AMPK Amplifies IL2-STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

T-Lymphocytes, Regulatory* ; STAT5 Transcription Factor*/genetics ; STAT5 Transcription Factor*/metabolism; Mice ; Animals ; Interleukin-2/genetics ; Interleukin-2/metabolism ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Mice, Knockout ; Forkhead Transcription Factors/metabolism

AMP-activated protein kinase (AMPK), an important regulator of the aging process, is expressed in various immune cells. However, its role in regulatory T cell (Treg) stability during aging is poorly understood. Here, we addressed the role of AMPK in Treg function and stability during aging by generating Treg-specific AMPKα1 knockout mice. In this study, we found that AMPKα1-deficient Tregs failed to control inflammation as effectively as normal Tregs did during aging. AMPK knockout from Tregs reduces STAT5 phosphorylation in response to interleukin (IL)-2 stimulation, thereby destabilizing Tregs by decreasing CD25 expression. Thus, our study addressed the role of AMPK in Tregs in sensing IL-2 signaling to amplify STAT5 phosphorylation, which, in turn, supports Treg stability by maintaining CD25 expression and controlling inflamm-aging.

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222A380011 Yeungnam University Research Grant

Keywords: AMPK; Treg stability; aging; inflammation

0 (STAT5 Transcription Factor)
0 (Interleukin-2)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
0 (Forkhead Transcription Factors)

Date Created: 20221027 Date Completed: 20221028 Latest Revision: 20221030

20250114

PMC9604214

10.3390/ijms232012384

36293240