Biochimica et biophysica acta. Molecular basis of disease · 2025
Inflammatory and tolerogenic dendritic cells and T lymphocytes in Graves' thyroidal and orbital disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Zeiträg Julia, Benedicic Manuela, Wolf Jan, Ammon Tim, Mayr Vanessa, Holthoff Hans-Peter, Kahaly George J, Ungerer Martin
Аннотация
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.
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.