Kong X, et al. - Since prior work exhibited a genetic correlation between Takayasu arteritis and a non-coding genetic variant in an enhancer region within IL6 (rs2069837 A/G) and the risk allele in this variant (allele A) has a protective influence against chronic viral infection and cancer, a combination of experimental and bioinformatics tools were used by the researchers to identify the functional consequences of this disease-associated risk locus. The monocyte/macrophage anti-inflammatory gene GPNMB,~520 kb from IL6, as a target gene regulated by rs2069837 was recognized. The preferential recruitment of myocyte enhancer factor 2–histone deacetylase (MEF2–HDAC) repressive complex to the Takayasu arteritis risk allele was demonstrated. Suppression of GPNMB expression in monocyte-derived macrophages from healthy people with AA compared with AG genotype, which was reversed by histone deacetylase inhibition was exhibited. By recruiting MEF2–HDAC complex, the risk allele in rs2069837 inhibited the expression of GPNMB enabled through a long-range interchromatin looping. In Takayasu arteritis, the suppression of this anti-inflammatory gene might mediate elevated susceptibility and improve protective immune responses in chronic infection and cancer. Therefore, by suppression of the anti-inflammatory gene GPNMB through chromatin looping and recruitment of MEF2–HDAC epigenetic repressive complex, Takayasu arteritis risk locus in IL6 might enhance disease susceptibility. Moreover, long-range chromatin interactions in functional genomic and epigenomic studies in autoimmunity was reflected.