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

Daniel Álvarez-Sierra1,2, Ana Marín-Sánchez1,2, Aroa Gómez-Brey3

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This study reveals that autoimmune thyroiditis involves complex immune cell interactions, with naive B cells and M2 macrophages playing significant roles in disease progression and immune suppression.

Keywords:
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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.