Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [array]. Mus musculus

Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown. Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients. Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity. Overall design: Microarray expression data of mouse bone marrow derived macrophages containing shRNA derived knockdown of SP140 or not, and stimulated with LPS (100ng/mL, 4h) or not. N=3 for each condition.