Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders.
J Allergy Clin Immunol
; 2024 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-39098508
ABSTRACT
BACKGROUND:
Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear.OBJECTIVE:
We sought to understand spatial gene expression characteristics in these disorders.METHODS:
We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion.RESULTS:
CS is characterized by a polarized, spatially organized type 1-predominant response with classical macrophage activation. GA is characterized by a mixed but spatially organized pattern of type 1 and type 2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of type 1, type 2, and type 3 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation.CONCLUSIONS:
Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2024
Tipo de documento:
Article