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      [The Immunosuppressive Function of Myeloid-derived Suppressor Cells Is Regulated by the HMGB1-TLR4 Axis].

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          Abstract

           Myeloid-derived suppressor cells (MDSCs) accumulate under pathological conditions, including cancer and chronic inflammation, and they suppress various immune responses such as T cell proliferation. Although several inflammatory signals enhance the differentiation and/or function of MDSCs, it is not clear which factors regulate their differentiation and immunosuppressive function. It has been highlighted that damage-associated molecular patterns (DAMPs) play important roles in the induction of inflammation. One of the DAMPs, the high mobility group box 1 (HMGB1), is released from necrotic cells and secreted by macrophages. It has been shown that HMGB1 level is elevated in tumors and tumor-bearing hosts. It has also been reported that HMGB1 transduces intracellular signaling via several receptors, including the receptor for advanced glycation end-products (RAGE) and the toll-like receptor (TLR)4, both of which enhance the differentiation and/or function of MDSCs. However, the effects of HMGB1 on MDSCs remain unclear. In the present study, we examined the effect of HMGB1 on in vitro MDSC differentiation and immunosuppressive functions. Since murine bone marrow (BM) cells can differentiate into MDSCs upon granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation for 4 d in vitro, we cultured murine BM cells in the presence of HMGB1 and GM-CSF. The results demonstrated that HMGB1 enhanced the suppressive activity of in vitro MDSCs, depending on TLR4, whereas lipopolysaccharide (LPS), one of the TLR4 ligands, interfered with this differentiation and immunosuppressive activity of in vitro MDSCs, depending on TLR4. Our findings thus suggest that the HMGB1-TLR4 axis enhances the immunosuppressive function of MDSCs.

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          Author and article information

          Journal
          Yakugaku Zasshi
          Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
          Pharmaceutical Society of Japan
          1347-5231
          0031-6903
          2018
          : 138
          : 2
          Affiliations
          [1 ] Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University.
          [2 ] Global Center for Medical Engineering and Informatics, Osaka University.
          Article
          10.1248/yakushi.17-00158
          29386427
          36ea9023-1f5a-4556-96d8-f5258a18f21a
          History

          high mobility group box 1,myeloid-derived suppressor cell,toll-like receptor 4

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