CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(2021)
Abstract
CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38(+)CD25(+) T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38(+) regulatory T-cells are more suppressive than CD38(-) regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Fas(lpr)/J). Additionally, B6.MRL-Fas(lpr)/J mice showed a decreased proportion of CD38(+) Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-gamma/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.
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Key words
CD38, regulatory T-cells, systemic lupus erythematosus, immunosuppressive, lupus-prone mice, IFN-gamma, IL-10
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