RESUMEN
Hashimoto's thyroiditis (HT) is the most common autoimmune disease characterized by lymphocytic infiltration and thyrocyte destruction. Dissection of the interaction between the thyroidal stromal microenvironment and the infiltrating immune cells might lead to a better understanding of HT pathogenesis. Here we show, using single-cell RNA-sequencing, that three thyroidal stromal cell subsets, ACKR1+ endothelial cells and CCL21+ myofibroblasts and CCL21+ fibroblasts, contribute to the thyroidal tissue microenvironment in HT. These cell types occupy distinct histological locations within the thyroid gland. Our experiments suggest that they might facilitate lymphocyte trafficking from the blood to thyroid tissues, and T cell zone CCL21+ fibroblasts may also promote the formation of tertiary lymphoid organs characteristic to HT. Our study also demonstrates the presence of inflammatory macrophages and dendritic cells expressing high levels of IL-1ß in the thyroid, which may contribute to thyrocyte destruction in HT patients. Our findings thus provide a deeper insight into the cellular interactions that might prompt the pathogenesis of HT.
Asunto(s)
Microambiente Celular/inmunología , Enfermedad de Hashimoto/metabolismo , Linfocitos/metabolismo , Células Epiteliales Tiroideas/metabolismo , Glándula Tiroides/metabolismo , Enfermedades Autoinmunes/metabolismo , Quimiocina CCL21/metabolismo , Citocinas/metabolismo , Sistema del Grupo Sanguíneo Duffy , Células Endoteliales/metabolismo , Humanos , Interleucina-1beta , Células Mieloides , Receptores de Superficie Celular , Glándula Tiroides/patologíaRESUMEN
This paper presents a novel front-illuminated InAlAs/InGaAs separate absorption, grading, field-control and multiplication (SAGFM) avalanche photodiodes (APDs) with a mesa-structure for high speed response. The electric fields in the InAlAs-multiplication layer and InGaAs-absorption layer enable high multiplication gain and high-speed response thanks to the thickness and concentration of the field-control and multiplication layers. A mesa active region of 45 micrometers was defined using a bromine-based isotropic wet etching solution. The side walls of the mesa were subjected to sulfur treatment before being coated with a thick polyimide layer to reduce current leakage, while lowering capacitance and increasing response speeds. The breakdown voltage (VBR) of the proposed SAGFM APDs was approximately 32 V. Under reverse bias of 0.9 VBR at room temperature, the proposed device achieved dark current of 31.4 nA, capacitance of 0.19 pF and multiplication gain of 9.8. The 3-dB frequency response was 8.97 GHz and the gain-bandwidth product was 88 GHz. A rise time of 42.0 ps was derived from eye-diagrams at 0.9 VBR. There was notable absence of intersymbol-interference and the signals remained error-free at data-rates of up to 12.5 Gbps.