Journal of Endocrinology

Thyroid hormone enhances dendritic cell maturation and function. In dendritic cells, T₃ enters the cell via TH transporters MCT10 or LAT2 and binds to cytoplasmic TRβ1 (Gigena et al. 2015 abstract 475, presented at the International Thyroid Congress). Upon binding of T₃, TRβ1 translocates from the cytoplasm to the nucleus (Mascanfroni et al. 2008, 2010). T₃ binding to TRβ1 also activates cytoplasmic NFκB by initiating degradation of IκB so that NFκB can translocate to the nucleus and regulate gene transcription, including induction of TRβ1 transcription, which is an NFκB target gene, thus forming a regulatory feedback loop controlling TRβ1 levels (Mascanfroni et al. 2008). Furthermore, binding of T₃ to cytoplasmic TRβ1 activates the Akt pathway, leading to a nuclear shift of phosphorylated Akt and increased chemokine (C–C motif) receptor type 7 (CCR7) expression, which prolongs cell viability and augments cell migration towards lymph nodes (Mascanfroni et al. 2010, Alamino et al. 2015). T₃ stimulation of DCs shifts the cells towards a more pro-inflammatory phenotype through induction of cell maturation, increased IL-12 production, improved antigen cross presentation and an enhanced ability to stimulate a cytotoxic T-cell response and trigger antigen-specific responses in vivo (Mascanfroni et al. 2008, 2010, Alamino et al. 2015, 2016).