Lymphocytic Thyroiditis Transcriptomic Profiles Support the Role of Checkpoint Pathways and B Cells in Pathogenesis

Area of Science:

• Immunology
• Genomics
• Pathology

Background:

• Autoimmune thyroid diseases are common but poorly understood.
• The Genotype-Tissue Expression (GTEx) dataset offers valuable thyroid RNA-seq data.
• Thyroid samples in GTEx show varying degrees of lymphocytic infiltration.

Purpose of the Study:

• To characterize infiltrating immune cells in autoimmune thyroiditis.
• To identify novel molecular pathways involved in thyroid autoimmunity.
• To analyze transcriptomic changes in relation to thyroid infiltration levels.

Main Methods:

• Histological classification of 336 thyroid samples into non-infiltrated, small focal infiltrated, and extensive lymphoid infiltrated categories.
• Differential gene expression analysis and pathway enrichment analysis.
• Cell type deconvolution using CIBERSORTx to quantify infiltrating immune cells.

Main Results:

• Transcriptional changes correlate with tissue infiltration levels.
• Upregulated genes include immune checkpoint receptors on B and T cells.
• T cells predominate over B cells, with increased follicular helper, memory CD4 T cells, and a significant rise in naive B cells in highly infiltrated glands.
• M2 macrophages are more abundant than M1 and M0 subtypes across all infiltration levels.

Conclusions:

• Active autoimmune responses in thyroid glands are accompanied by counteracting suppressor mechanisms.
• Glands with small infiltrates show a surprisingly high proportion of B lymphocytes.
• Highly infiltrated glands exhibit transcriptomic signatures of active tertiary lymphoid organs, suggesting amplified autoimmune responses.