한빛사논문
- 조회1,446
Min-Seok Rha1, Ji Won Han1, Jong Hoon Kim1,2, June-Young Koh1, Hye Jung Park3, Soon Il Kim4, Myoung Soo Kim4, Jae Geun Lee4, Hyun Woong Lee5, Dong Hyeon Lee6, Won Kim6, Jun Yong Park3, Dong Jin Joo4,*, Su-Hyung Park1,*, Eui-Cheol Shin1,*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
2Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
3Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
4Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
5Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
6Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea
*Corresponding author
Abstract
Background & Aims
Mucosal-associated invariant T (MAIT) cells, the most abundant innate-like T cells in human liver, can be activated by cytokines during viral infection without TCR stimulation. Here, we examined the mechanisms underlying TCR/MR1-independent innate-like cytotoxicity of cytokine-activated liver MAIT cells. We also examined the phenotype and function of MAIT cells from patients with acute viral hepatitis.
Methods
We obtained liver sinusoidal mononuclear cells from donor liver perfusate during liver transplantation and examined the effect of various cytokines on liver MAIT cells using flow cytometry and in vitro cytotoxicity assays. We also obtained peripheral blood and liver-infiltrating T cells from patients with acute hepatitis A (AHA) and examined the phenotype and function of MAIT cells using flow cytometry.
Results
IL-15-stimulated MAIT cells exerted granzyme B-dependent innate-like cytotoxicity in the absence of TCR/MR1 interaction. PI3K–mTOR signaling, NKG2D ligation, and CD2-mediated conjugate formation were critically required for this IL-15-induced innate-like cytotoxicity. MAIT cells from patients with AHA exhibited activated and cytotoxic phenotypes with higher NKG2D expression. The innate-like cytotoxicity of MAIT cells was significantly increased in patients with AHA and correlated with serum alanine aminotransferase levels.
Conclusions
Taken together, the results demonstrate that liver MAIT cells activated by IL-15 exert NKG2D-dependent innate-like cytotoxicity in the absence of TCR/MR1 engagement. Furthermore, the innate-like cytotoxicity of MAIT cells is associated with liver injury in patients with AHA, suggesting that MAIT cells contribute to immune-mediated liver injury in liver disease.
Keywords : Mucosal-associated invariant T cells; IL-15; Cytotoxicity; Hepatitis; Virus
논문정보
- Research article
- 2020년 04월 (BRIC 등록일 2020-04-07)
- 국내 연구진
- 의약학 > 면역의학
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