Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution

[helvella]

This appears to be an amazing paper - if you want to understand exactly what happens, where, in Graves' Disease and Hashimoto's Thyroiditis. Incredible number of images, lots of text - needs a slightly darkened room and lots of time!

I've only just seen it so have nothing more to add at this stage.

When I view it, I see a series of images and text just below the abstract headed: Similar content being viewed by others

They might also be worth a read.

Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution

Rebeca Martínez-Hernández, Nuria Sánchez de la Blanca, Pablo Sacristán-Gómez, Ana Serrano-Somavilla, José Luis Muñoz De Nova, Fátima Sánchez Cabo, Holger Heyn, Miguel Sampedro-Núñez & Mónica Marazuela

Nature Communications volume 15, Article number: 5895 (2024)

Abstract

Autoimmune thyroid diseases (AITD) such as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF+ myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD.

Open access to full paper:

nature.com/articles/s41467-...

Suggestion:

I suggest reading the abstract and the discussion. Going back to the rest as and when you feel a desperate urge to do so!

Abbreviations:

As I come across unusual or difficult acronyms/abbreviations, I'm adding them below to help anyone trying to read the paper!

ADIRF = Adipogenesis Regulatory Factor

DCN = decorin

ECM = extracellular matrix

IAF = inflammatory associated fibroblasts

MIF = macrophage migration inhibitory factor

PAX8 = Paired box gene 8, is a protein which in humans is encoded by the PAX8 gene.

PCA = Principal Component Analysis

PLVAP = Plasmalemma Vesicle Associated Protein

SMA = smooth muscle actin

SMC = smooth muscle cells (SMCs)

TAGLN = Tagln OE /Tagln sh fibroblasts

TDS = Thyrocyte Differentiation Score

TFC = thyroid follicular cells (TFCs)

TIL = thyroid infiltrating lymphocytes (TILs)

UMAP = Uniform Manifold Approximation and Projection

[tattybogle]

Thanks perfect timing ~

was looking for something to occupy myself with that doesn't require me to pretend to be excited about football......

[helvella Administrator Thyroid UK in reply to tattybogle]

I think it could occupy more than 45 minutes each way, half-time, extra time and injury time plus penalty shoot-out!

Even if you add hours of repetitive re-showing of clips, commentary, medal awards, etc., etc.

[Jspringer]

Thank you ❤️

[buddy99]

Thank you. This looks like it will keep me busy and my head spinning for a couple of years.

[helvella Administrator Thyroid UK in reply to buddy99]

It's tough going!

However, the fact that it is so incredibly complicated makes a nonsense of "the antibodies attack the thyroid" as a complete explanation.

One sentence quite near the start says:

From the pathological point of view, HT [Hashimoto's Thyroiditis] exhibits a rich lymphocytic infiltrate commonly located in follicles with germinal center. Lymphocytes are predominantly T cells along with numerous B lymphocytes and macrophages polarized to an inflammatory phenotype.

That is, "it's the lymphocytes wot dun it". As has been said here numerous times over the years.

[Judithdalston in reply to helvella]

Brain fog means get bogged down after first dozen words…thought perhaps images might be easier, but no…too many abbreviations and can’t work out how bits relate to other bits. Hopeless!

[helvella Administrator Thyroid UK in reply to Judithdalston]

The article does have lots of diagrams!

nature.com/articles/s41467-...

But I'll not pretend even they are easy to follow. Bits are but having a mental awareness of what the bits are in the diagram is important to enable understanding.

And don't think for one moment I have got beyond a few stumbling bits of understanding!

[buddy99]

It's definitely worth chomping my way through. I put it in my file for further perusal. There were a couple of things that caught my eye (just the one....it's 3 am here and the other eye is sleeping). Thanks again for sharing. It's a keeper.

[jiankang]

thank you for sharing

[jacksnipe]

A definite print out. Thank you Helvella.

[Bertwills]

Without the knowledge to fully understand it, it think it shows how much is affected by Hashi’s & by hypothyroidism. It’s definitely not a simple mater & definitely not completely put right for many by taking a little white pill everyday.