Regulatory T Cells Molecular Defects in SLE.

What is it about?

Systemic Lupus Erythematosus (SLE) is characterized by a wide array of defects in peripheral immune tolerance mechanisms, as resistance to supression by regulatory T cells. The aim of the present to study was to assess the role of ubiquitin ligase Cbl-b in this phenomenum. We isolated regulatory T cells from 30 SLE patients as well as 30 healthy controls and performed suppression assays in autologous and allogenic co-cultures. Moreover, we studied Cbl-b expression and lysine-63 (K63)-specific polyubiquitination profile by Western blotting. We found a defective expression of Cbl-b in regulatory T cells from lupus patients related to healthy controls, which was associated with resistance to suppression. Likewise, this characteristic was associated with deficient K63 polyubiquitination substractes and enhaced expression of phosphorylated signal transducer and activation of transcription 3 (pSTAT-3). Our data suggest that Cbl-b modulates resistance to suppression and polyubiquitination profile in Tregs from lupus patients, which at the same time may promote their polarization to an effector phenotype.

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Why is it important?

We are the first group to demostrate that regulatory T cells from lupus patients do not have a intact suppressive capacity as previously described, and present a wide array of molecular defects which may promote their polarization to an effector phenotype. Moreover, our study underscores the crucial role of ubiquitination system in immune tolerance mechanisms anomalies in autoimmune diseases. .

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