Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus

• Published in: PloS one Vol. 11; no. 8; p. e0161682
• Main Authors: Orme, Jacob J., Du, Yong, Vanarsa, Kamala, Wu, Tianfu, Satterthwaite, Anne B., Mohan, Chandra
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.08.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Autoimmune diseases; Autoimmunity; Axin Protein - genetics; Axin Protein - immunology; Axin Protein - metabolism; beta Catenin - deficiency; beta Catenin - genetics; beta Catenin - immunology; Biology and Life Sciences; Biomedical engineering; Care and treatment; Cell adhesion & migration; Chronic conditions; Clonal deletion; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Diagnosis; Disease; Disease Models, Animal; Dkk1 protein; Drosophila; Engineering; Female; Follistatin-Related Proteins - genetics; Follistatin-Related Proteins - immunology; Follistatin-Related Proteins - metabolism; Gene Deletion; Gene Expression Regulation; Hepatocellular carcinoma; Human subjects; Humans; Immunity; Immunology; Inflammation; Insects; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Internal medicine; Kidneys; Leukocytes; Leukocytes - immunology; Leukocytes - pathology; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Macrophages; Macrophages - immunology; Macrophages - pathology; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Myeloid cells; Patients; Preempting; Research and Analysis Methods; Rheumatic diseases; Rodents; Serum levels; Signaling; Spleen - immunology; Spleen - pathology; Systemic lupus erythematosus; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - immunology; Wnt Proteins - metabolism; Wnt Signaling Pathway; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161682

Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus. Although myeloid-specific loss of β-catenin does not seem to be important for lupus development, the potential role of this transcription factor in other leukocytes and renal cells remain to be elucidated.