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

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. 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.