Indole-3-carbinol improves survival in lupus-prone mice by inducing tandem B- and T-cell differentiation blockades

• Published in: Clinical immunology (Orlando, Fla.) Vol. 131; no. 3; pp. 481 - 494
• Main Authors: Yan, Xiao-jie, Qi, Mei, Telusma, Gloria, Yancopoulos, Sophia, Madaio, Michael, Satoh, Minoru, Reeves, Westley H, Teichberg, Saul, Kohn, Nina, Auborn, Karen, Chiorazzi, Nicholas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.06.2009; Elsevier
• Subjects: Administration, Oral; Allergy and Immunology; Animals; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Autoantibodies; Autoantibodies - drug effects; Autoantibodies - immunology; B lymphocytes; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cytokines; Cytokines - biosynthesis; Cytokines - drug effects; Cytokines - immunology; Disease Models, Animal; Estrogen; Estrogens - metabolism; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; I3C; Immunoglobulin G - biosynthesis; Immunoglobulin G - drug effects; Immunoglobulin G - immunology; Indoles - pharmacology; Indoles - therapeutic use; Kaplan-Meier Estimate; Longitudinal Studies; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - mortality; Lymphocyte maturation; Medical sciences; Mice; Nephritis - drug therapy; Nephritis - immunology; Nephritis - mortality; Renal disease; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; SLE; Systemic lupus erythematosus; T lymphocytes; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T lymphocytes; 2-OH; Autoantibodies; Cytokines; B lymphocytes; 2-hydroxylated; Estrogen; Indole-3-carbinol; 16α-hydroxylated; Renal disease; SLE; Lymphocyte maturation; Systemic lupus erythematosus; I3C; 16α-OH; Autoimmunity; Animal model; Skin disease; Autoimmune disease; Immunology; Systemic disease; T-Lymphocyte; Kidney disease; Immunopathology; Connective tissue disease; 13C; Urinary system disease; Antibody; Rodentia; Cytokine; Autoantibody; B-Lymphocyte; Cell differentiation; Survival; Ovarian hormone; Vertebrata; Mammalia; Nephropathy; Mouse; Animal; Sex steroid hormone
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.01.013

Abstract Indole-3-carbinol (I3C), derived from cruciferous vegetables, alters estrogen metabolism. Since lupus is estrogen dependent, we reasoned that I3C might be effective in SLE. I3C significantly thwarted disease progression and prolonged survival in (NZB × NZW) F1 mice. Immunofluorescent and serologic analyses in treated animals indicated a transient blockade in B-cell maturation with increased immature B cells, decreased mature B cells, and a significant reduction of certain autoantibodies. Subsequently, a delay in T-cell maturation occurred in the treated group, manifested by significantly increased naive T cells, decreased mature and memory T cells, and decreased CD4:CD8 T-cell ratios. T cells from the I3C cohort, stimulated in vitro with various mitogens, exhibited enhanced responsiveness. Con A-stimulated T cells from I3C-treated mice produced Th1 cytokines, whereas those from control animals produced Th2 cytokines. Our studies suggest immunological mechanisms by which I3C ameliorates SLE in mice and provide a rationale for its use as an adjunctive therapy for human lupus.