title: Indole-3-carbinol improves survival in lupus-prone mice by inducing tandem B- and T-cell differentiation blockades.
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 (NZBxNZW) 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.
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Yan
authors.forename: Mei
authors.initials: M
authors.lastname: Qi
authors.forename: Gloria
authors.initials: G
authors.lastname: Telusma
authors.forename: Sophia
authors.initials: S
authors.lastname: Yancopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Madaio
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Saul
authors.initials: S
authors.lastname: Teichberg
authors.forename: Nina
authors.initials: N
authors.lastname: Kohn
authors.forename: Karen
authors.initials: K
authors.lastname: Auborn
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051379:Mice; D009393:Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D001323:Autoantibodies; D016207:Cytokines; D004967:Estrogens; D007074:Immunoglobulin G; D007211:Indoles; C016517:indole-3-carbinol