Figure 7.

A model of neutral thyrotropin receptor antibody (N-TSHR-mAb) action on fibroblasts. After endocytosis of N-TSHR-mAb/TSHR complexes into the cytoplasm of cells, there is no cyclic adenosine monophosphate (cAMP) generation but rather reactive oxygen species induction in the mitochondria due to the lack of cAMP/PKA/PI3K/Akt signaling molecules. Both mitochondria and the endoplasmic reticulum undergo stress and have compromised function leading to mitochondrial DNA damage together and failure of autophagy to protect the cells. These effects cause activation of inflammasomes via NLRP3/AIM-2/Casp1/ASC signaling cascades leading to the activation of Casp-8 and gasdermin-D (GSDM-D), ultimately causing cell death by pyroptosis and interleukin (IL)-1β secretion.