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Epigenetic Modification Mediates the Increase of LAG-3+ T Cells in Chronic Osteomyelitis

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ABSTRACT

Immune suppression plays critical roles in the development of chronic osteomyelitis, and the mechanisms underlying the development of immune suppression in chronic osteomyelitis have attracted much attention. LAG-3 is an important suppressor of T cell activation, but the role of LAG-3 in the immune regulation of chronic osteomyelitis is currently unknown. We sought to demonstrate if LAG-3 plays crucial roles in chronic osteomyelitis progression and has effects on immune suppression and exhausting of T cells, and what is the mechanism underlying LAG-3 deregulation in chronic osteomyelitis. We examined the expression of LAG-3 in the T cells of peripheral blood of 50 healthy controls and 50 patients with chronic osteomyelitis by flow cytometry. Clinical data were analyzed to determine the correlation between inflammation index and LAG-3 expression. Moreover, we isolated the CD4+ T cells from healthy controls and chronic osteomyelitis patients to compare cell proliferation and IFN-γ production. Chromatin immunoprecipitation assays were utilized to analyze the epigenetic modification on LAG-3 expression in T cells. We found that LAG-3 was significantly increased in the T cells of peripheral blood from chronic osteomyelitis patients. Subsequently, clinical data analysis suggested that the higher expression of LAG-3 was associated with severer inflammation situation. Consistently, LAG-3+CD4+ T cells exhibited impaired cell proliferation and IFN-γ secretion. Deregulation of histone methylation mediated the increase of LAG-3+ T cells during chronic osteomyelitis. Taken together, our study demonstrates the increase of LAG-3+ T cells and its immune regulatory roles in chronic osteomyelitis progression, suggesting new mechanisms and potential therapeutic targets for chronic osteomyelitis.

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ACKNOWLEDGEMENTS

The authors thank National Nature Science Foundation of China (Grant No. 81500290) for the financial support.

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    Authors and Affiliations

    1. Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China

      Yicun Wang, Jun Wang, Jia Meng, Hui Jiang, Jianning Zhao & Hongbo Qian

    2. Cardiology Department of Chinese PLA General Hospital, 28# Fuxing Road, Haidian District, Beijing, China

      Tao Chen

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    1. Yicun Wang
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    2. Jun Wang
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    3. Jia Meng
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    4. Hui Jiang
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    Correspondence to Hongbo Qian or Tao Chen.

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    Tao Chen has received research support funding from National Nature Science Foundation of China (Grant No. 81500290).

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    Both Yicun Wang and Jun Wang have equal contributions and are co-first author.

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    Wang, Y., Wang, J., Meng, J. et al. Epigenetic Modification Mediates the Increase of LAG-3+ T Cells in Chronic Osteomyelitis. Inflammation 40, 414–421 (2017). https://doi.org/10.1007/s10753-016-0486-0

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