Photo Credit: Krblokhin

The following is a summary of “Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders,” published in the August 2024 issue of Allergy and Immunology by Daccache et al.

Non-infectious cutaneous granulomatous disorders, including cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG), are characterized histologically by macrophage-dominant inflammation, though they exhibit distinct variations in inflammatory architecture and extracellular matrix alterations. The molecular basis for these differences still needs to be better understood.

This study aimed better to elucidate these disorders’ spatial gene expression profiles to understand their immune activation patterns and molecular features.

Researchers employed spatial transcriptomics to analyze tissue samples from patients with CS, GA, NL, and NXG. This approach allowed them to assess immune activation patterns and other molecular characteristics within their spatial contexts.

The analysis revealed that CS is marked by a highly organized, polarized T helper (Th) 1 response with classical macrophage activation. In contrast, GA exhibited a mixed but spatially structured Th1 and Th2 polarization alongside classical and alternative macrophage activation. NL displayed concurrent activation of Th1, Th2, and Th17 pathways with a heterogeneous macrophage activation pattern. Shared between CS, GA, and NL was the activation of type 1 immunity, notably including the upregulation of IL-32. NXG, on the other hand, was associated with increased CXCR4-CXCL12/14 chemokine signaling and pronounced alternative macrophage polarization. Histological changes in the extracellular matrix were linked to programs of hypoxia and glycolysis and were associated with type 2 immune activation.

The study demonstrates that inflammatory cutaneous granulomatous disorders exhibit distinct and spatially organized immune activation patterns, which correlate with their characteristic histological features. Understanding these molecular and spatial differences enhances the knowledge of these disorders and may inform more targeted therapeutic approaches.

Source: sciencedirect.com/science/article/abs/pii/S0091674924007784