Analysis of under-expressed genes complemented the portrait of generalized immune activation in showing reduced expression of cell cycle inhibitors (CDKN1C, CSPG6, p15/PAF/KIAA0101, SPARC, FKBP5), apoptosis-related genes (MCL1, BIRC1, HSXIAPAF1, and TNFSF10/TRAIL), the antiproliferative cytokine TGF-β (TGFB1), and the NF-κB inhibitor Apo J (CLU). However, several specific dimensions of immune response showed selective repression against this generalized backdrop of immune activation. Genes involved in type I interferon response were down-regulated, including the signal transducer STAT1 and the interferon response genes 2',5'-oligoadenylate synthetase 1 (OAS1), interferon-stimulated gene 12 (IFI27), interferon-induced protein 6-16 (G1P3), and interferon-inducible proteins 15 and 44 (G1P2, IFI44). Also down-regulated were genes encoding immunoglobulin light, joining, and heavy region chains (IGLC2, IGLL1, IGK/IGKC/IGKGV, IGJ, IGLJ3, IGHG1, IGHM), B lymphocyte maturation markers (CD79B, CD269/TNFRSF17), and transcription fators involved in B cell differentiation (Ikaros/ZNFN1A1, POU2AF1). Thus, the circulating leukocyte complement in chronically lonely individuals shows broad genomic indications of immune activation and pro-inflammatory signaling accompanied by selective reductions in mature B lymphocyte function and innate antiviral responses.
