4.7 Article

CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice

Journal

Publisher

MDPI
DOI: 10.3390/ijms222111977

Keywords

CD38; regulatory T-cells; systemic lupus erythematosus; immunosuppressive; lupus-prone mice; IFN-gamma; IL-10

Funding

  1. CONACYT [214, A1-S-26657, CONACYT 284961, 253138]

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CD38 is a transmembrane glycoprotein expressed by T-cells and may play a role in regulating immune activation cells in SLE patients. Studies have found correlations between CD38 and regulatory T-cells as well as immunosuppressive molecules, suggesting that CD38 deficiency could enhance autoimmunity development. Additionally, CD38 appears to be crucial in maintaining activated and proliferative Treg cells, potentially preventing SLE development through Treg cells.
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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