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최진경Jin Kyeong Choi
전북대학교 의과대학
J. Allergy Clin. Immunol., July 06, 2026 | https://doi.org/10.1016/j.jaci.2026.06.015
AMPK-driven immunometabolic reprogramming enhances CD19+CD21hiCD24hi regulatory B cell-mediated suppression of atopic dermatitis
Seung Taek Lee, MS1 ∙ Ha Eun Kim, MS1 ∙ So-Yeon Kim, MS2,5 ∙ Jong Yeong Lee, PhD1 ∙ Kyung-Hwa Nam, MD, PhD2,5 ∙ Sang-Hyun Kim, PhD3 ∙ Jun-Young Park, PhD4 ∙ Jin Kyeong Choi, PhD1,5
1Department of Immunology, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea
2Department of Dermatology, College of Medicine, Jeonbuk National University, Jeonju, 54907, Republic of Korea
3CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
4Department of Biochemistry, Chungbuk National University, Cheongju, 28644, Republic of Korea
5Biomedical Research Institute of Jeonbuk National University Hospital, Institute for Medical Sciences, Jeonbuk National University
Corresponding author: Prof. Jin Kyeong Choi, PhD
1Department of Immunology, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea
2Department of Dermatology, College of Medicine, Jeonbuk National University, Jeonju, 54907, Republic of Korea
3CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
4Department of Biochemistry, Chungbuk National University, Cheongju, 28644, Republic of Korea
5Biomedical Research Institute of Jeonbuk National University Hospital, Institute for Medical Sciences, Jeonbuk National University
Corresponding author: Prof. Jin Kyeong Choi, PhD
Abstract
Background
Atopic dermatitis (AD) is characterized by dysregulated immune responses and persistent inflammation. Regulatory B cells (Bregs) suppress inflammation, but the metabolic mechanisms constraining their function in AD remain unclear.
Objective
We sought to define whether immunometabolic regulation governs Breg differentiation and function in AD.
Methods
Mouse and human B cells were stimulated with the AMPK activator AICAR under inflammatory conditions, with genetic and pharmacologic perturbations. Functional and mechanistic analyses were performed using co-culture systems, a 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced murine model of AD, adoptive transfer approaches, adoptive transfer, and human PBMCs from patients with AD.
Results
AICAR treatment or adoptive transfer of AICAR-induced Bregs significantly attenuated AD-like inflammation, whereas AMPK inhibition or IL-10 blockade abrogated these effects. Mechanistically, AICAR induced IL-10-producing Bregs through AMPK-dependent suppression of mTOR signaling and mitochondrial reactive oxygen species while preserving oxidative phosphorylation. This reprogramming selectively enhanced regulatory B cell function and suppressed STAT1 signaling without affecting STAT3. Functionally, these Bregs suppressed Th1, Th2, and Th17 responses in an IL-10-dependent manner without expanding Foxp3+ regulatory T cells. In human PBMCs from patients with AD, AICAR restored immunometabolic coupling by increasing IL-10-producing B cells and reducing pro-inflammatory cytokine production.
Conclusion
These findings identify an AMPK-mTOR-redox metabolic checkpoint that governs regulatory B cell function and restrains AD inflammation, linking metabolic control to immune regulation.
Atopic dermatitis (AD) is characterized by dysregulated immune responses and persistent inflammation. Regulatory B cells (Bregs) suppress inflammation, but the metabolic mechanisms constraining their function in AD remain unclear.
Objective
We sought to define whether immunometabolic regulation governs Breg differentiation and function in AD.
Methods
Mouse and human B cells were stimulated with the AMPK activator AICAR under inflammatory conditions, with genetic and pharmacologic perturbations. Functional and mechanistic analyses were performed using co-culture systems, a 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced murine model of AD, adoptive transfer approaches, adoptive transfer, and human PBMCs from patients with AD.
Results
AICAR treatment or adoptive transfer of AICAR-induced Bregs significantly attenuated AD-like inflammation, whereas AMPK inhibition or IL-10 blockade abrogated these effects. Mechanistically, AICAR induced IL-10-producing Bregs through AMPK-dependent suppression of mTOR signaling and mitochondrial reactive oxygen species while preserving oxidative phosphorylation. This reprogramming selectively enhanced regulatory B cell function and suppressed STAT1 signaling without affecting STAT3. Functionally, these Bregs suppressed Th1, Th2, and Th17 responses in an IL-10-dependent manner without expanding Foxp3+ regulatory T cells. In human PBMCs from patients with AD, AICAR restored immunometabolic coupling by increasing IL-10-producing B cells and reducing pro-inflammatory cytokine production.
Conclusion
These findings identify an AMPK-mTOR-redox metabolic checkpoint that governs regulatory B cell function and restrains AD inflammation, linking metabolic control to immune regulation.
논문정보
- Research article
- 2026년 07월 (BRIC 등록일 2026-07-08)
- 국내 연구진
- 의약학 > 면역의학
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