High mobility group box 1 (HMGB1) is a small protein of 215 aa; it is a highly conserved protein in the nucleus, cytoplasm or extracellular environment (e.g., released from cells via necrosis and autophagy, secreted from inflammatory or cancer cells) with multiple distinguished functions. HMGB1 is highly expressed in tumour cells and its release may be associated with a greater tumour angiogenesis, growth, invasion and metastasis. This effect could be related to the ability of HMGB1 to inhibit DC function and CD8 T cell reactivity via enhancing T regulatory cells (Treg) to produce IL-10. However it is largely unknown whether and how HMGB1 acts on Tregs in physiological condition. In this study, we investigated whether hrHMGB1 has a direct effect on Tregs in human. Peripheral blood mononuclear cells (PBMCs), purified from buffy coats of healthy donors, were incubated in the absence or presence of hrHMGB1 (400 ng/ml) in medium containing low concentrations of IL-2 (2 ng/ml) and TNFα (50 ng/ml) to prevent Treg from spontaneous apoptosis. After 48 hours, the presence of CD4+CD25+Foxp3+ population was valuated by FACS analysis. We observed an increase of Treg cells in treated colture compared to PBMCs without hrHMGB1. We also evaluated the expression of CD39 on Tregs surface and the higher levels of this marker suggest a major efficiency in suppressor activity. HMGB1 does not seem to modulate directly the expression of its receptors on lymphocytes; in fact the levels of Toll-like receptor (TLR) 2, TLR4 and Receptor for Advanced Glycation Endproducts (RAGE) are similar in colture treated or not with hrHMGB1. This preliminary data suggest that hrHMGB1 is able to directly modulate the suppressive capacity of CD4+CD25+Foxp3+ Tregs.
High Mobility Group Box 1 (hmgb1) Expands CD4+CD25+Foxp3+ T Cells and Increases the Expression of CD39
SPONTON, LAURA;OCCHIPINTI, SERGIO;NOVELLI, Francesco;GIOVARELLI, Mirella
2011-01-01
Abstract
High mobility group box 1 (HMGB1) is a small protein of 215 aa; it is a highly conserved protein in the nucleus, cytoplasm or extracellular environment (e.g., released from cells via necrosis and autophagy, secreted from inflammatory or cancer cells) with multiple distinguished functions. HMGB1 is highly expressed in tumour cells and its release may be associated with a greater tumour angiogenesis, growth, invasion and metastasis. This effect could be related to the ability of HMGB1 to inhibit DC function and CD8 T cell reactivity via enhancing T regulatory cells (Treg) to produce IL-10. However it is largely unknown whether and how HMGB1 acts on Tregs in physiological condition. In this study, we investigated whether hrHMGB1 has a direct effect on Tregs in human. Peripheral blood mononuclear cells (PBMCs), purified from buffy coats of healthy donors, were incubated in the absence or presence of hrHMGB1 (400 ng/ml) in medium containing low concentrations of IL-2 (2 ng/ml) and TNFα (50 ng/ml) to prevent Treg from spontaneous apoptosis. After 48 hours, the presence of CD4+CD25+Foxp3+ population was valuated by FACS analysis. We observed an increase of Treg cells in treated colture compared to PBMCs without hrHMGB1. We also evaluated the expression of CD39 on Tregs surface and the higher levels of this marker suggest a major efficiency in suppressor activity. HMGB1 does not seem to modulate directly the expression of its receptors on lymphocytes; in fact the levels of Toll-like receptor (TLR) 2, TLR4 and Receptor for Advanced Glycation Endproducts (RAGE) are similar in colture treated or not with hrHMGB1. This preliminary data suggest that hrHMGB1 is able to directly modulate the suppressive capacity of CD4+CD25+Foxp3+ Tregs.
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