Panayotis Verginis, Investigator - Assistant Professor Level at BRFAA, recently published a paper with his colleagues in the Journal of Clinical Investigaton.  The article was also highlighted in Nature Reviews Rheumatology - Research Highlights.

Brief Overview of Publication

Autoimmune diseases arise when an immune response is directed against, and damage the body’s own tissue. The autoimmune response is mediated by self-reactive T cells that are present in all individuals and today we know that genetic predisposition as well as environmental factors contribute to their activation. Regulatory T cells (Tregs) are lymphocytes that their function is keep self-reactive T cells in check preventing therefore the development of autoimmunity. In this context, an aberrant function of regulatory T cells (Tregs) has been closely linked to development of autoimmune diseases and Treg-based therapies hold great promise for the treatment of autoimmunity. The clinical implementation of Treg-based therapies however has been hampered by various impediments due to lack of understanding on the mechanism of their action.

Our work identifies dendritic cell (DC) autophagy as a major target of Treg-mediated suppression. We showed that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte–associated protein 4–dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Importantly, human DCs treated with CTLA4-Ig, a fusion protein composed of the Fc region of IgG1 and the extracellular domain of CTLA4 (also known as abatacept, marketed as Orencia), demonstrated reduced levels of autophagosome formation, while DCs from CTLA4-Ig–treated rheumatoid arthritis patients displayed diminished autophagy.

These findings are clinically relevant and of potential therapeutic use since identification of innovative methods to efficiently target autophagy pathway in DCs could pave the way for the development of new therapies not only in the field of autoimmunity but also in transplantation.

Pubmed

JCI

Alissafi T, Banos A, Boon L, Sparwasser T, Ghigo A, Wing K, Vassilopoulos D, Boumpas D, Chavakis T, Cadwell K, Verginis P. Tregs restrain dendritic cell autophagy to ameliorate autoimmunity. J Clin Invest. 2017 Jun 5. pii: 92079. doi: 10.1172/JCI92079.