한빛사논문
- 조회468
Jiung Jeong1,2, In Kang1, Yumin Kim3, Keun Bon Ku1,4, Jang Hyun Park1, Hyun-Jin Kim1, Chae Won Kim1, Jeongwoo La1, Hi Eun Jung1, Hyeon Cheol Kim1, Young Joon Choi1, Jaeho Kim1, Joon Kim1 and Heung Kyu Lee1,3*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
2Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
3Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
4Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
*Corresponding author : Correspondence to Heung Kyu Lee.
Abstract
CD4+ T cells play major roles in the adaptive immune system, which requires antigen recognition, costimulation, and cytokines for its elaborate orchestration. Recent studies have provided new insight into the importance of the supramolecular activation cluster (SMAC), which comprises concentric circles and is involved in the amplification of CD4+ T cell activation. However, the underlying mechanism of SMAC formation remains poorly understood. Here, we performed single-cell RNA sequencing of CD4+ T cells left unstimulated and stimulated with anti-CD3 and anti-CD28 antibodies to identify novel proteins involved in their regulation. We found that intraflagellar transport 20 (IFT20), previously known as cilia-forming protein, was upregulated in antibody-stimulated CD4+ T cells compared to unstimulated CD4+ T cells. We also found that IFT20 interacted with tumor susceptibility gene 101 (TSG101), a protein that endocytoses ubiquitinated T-cell receptors. The interaction between IFT20 and TSG101 promoted SMAC formation, which led to amplification of AKT-mTOR signaling. However, IFT20-deficient CD4+ T cells showed SMAC malformation, resulting in reduced CD4+ T cell proliferation, aerobic glycolysis, and cellular respiration. Finally, mice with T-cell-specific IFT20 deficiency exhibited reduced allergen-induced airway inflammation. Thus, our data suggest that the IFT20-TSG101 axis regulates AKT-mTOR signaling via SMAC formation.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-11)
- 국내 연구진
- 생명과학 > 면역학
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