Inflammatory and tolerogenic dendritic cells and T lymphocytes in Graves' thyroidal and orbital disease.

BACKGROUND

Graves' disease (GD) and orbitopathy (GO) are common systemic autoimmune diseases targeting the human thyrotropin receptor. We carried out detailed immune cell investigations in GD/GO.

METHODS AND

RESULTS

For the first time, we describe inflammatory and tolerogenic dendritic cells (tolDCs) derived from GD/GO patient monocytes. GD/GO tolDCs show reduced inflammatory marker CD86 expression, but higher CD11c levels. CD86 expression on DCs correlates to anti-TSHR antibody titers in the patients. Release of interleukin-10 from GD/GO tolDCs is increased, and their phagocytotic capacity is maintained, whereas it is reduced in inflammatory DCs. We also characterise follicular T helper cells (Tfh) and detect significantly increased circulating Tfh17 in GD/GO. GD/GO Tfh cells were efficiently differentiated from CD4+ T cells in vitro.

CONCLUSIONS

Since DCs and Tfh are pivotal in B cell responses, these results are fundamental for future co-culture of disease-relevant germinal centres to model human GD/GO and test novel therapeutic approaches.