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Enhanced Level of Lysosomal associated membrane protein 2 isoform A Participates in CD4+ T Cell Hyperactivity in Patients with Primary Biliary Cholangitis
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  • Keshuai Sun,
  • Shuoyi Ma,
  • Siyuan Tian,
  • Miao Zhang,
  • Bo Li,
  • Xia Zhou,
  • Xiaohong Zheng,
  • Yansheng Liu,
  • Xinmin Zhou,
  • Lu Wang,
  • Ying Han
Keshuai Sun
Fourth Military Medical University
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Shuoyi Ma
Fourth Military Medical University
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Siyuan Tian
Fourth Military Medical University
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Miao Zhang
Fourth Military Medical University
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Bo Li
Fourth Military Medical University
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Xia Zhou
Fourth Military Medical University
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Xiaohong Zheng
Fourth Military Medical University
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Yansheng Liu
Fourth Military Medical University
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Xinmin Zhou
Fourth Military Medical University
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Lu Wang
Fourth Military Medical University
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Ying Han
Fourth Military Medical University
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Abstract

Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis. The disruption of T cell homeostasis plays an important role in PBC pathogenesis. Lysosomal associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4+ T cell responses, therefore we aim to evaluate the activation state of CD4+ T cells in PBC, and to investigate the role of LAMP-2A in it. The peripheral blood of PBC patients (PBC, n=42) and healthy controls (HC, n=20) were phenotypically analyzed, and LAMP-2A expression in CD4+ T cells was assessed by flow cytometry. Naïve CD4+ T cells of PBC patients were isolated and activated in vitro to estimate their activation responses. Additionally, we assessed the changes induced by silencing LAMP-2A expression. We found that CD4+ T cells of PBC patients exhibited significant hyperactivity, and naïve CD4+ T cells showed high LAMP-2A expression, which could be a novel biomarker for PBC activity. Moreover, by interfering with LAMP-2A expression in vitro, the overreactions of PBC naïve CD4+ T cells were reversed. Our study will help to clarify that increased LAMP-2A expression in the naïve CD4+ T cells of PBC patients may lead to a tendency for increased activation responses, which may be involved in the development and progression of PBC. To reverse the hyperactivity of CD4+ T cells and reduce the resulting biliary injury, LAMP-2A could be a novel therapeutic target for the treatment of PBC.

Peer review status:POSTED

28 Jan 2020Submitted to Clinical & Experimental Immunology
28 Jan 2020Assigned to Editor
28 Jan 2020Submission Checks Completed