title: Characterization of a recombinant Yersinia enterocolitica lipoprotein; implications for its role in autoimmune response against thyrotropin receptor.
abstract: Autoimmune Graves' disease (GD), which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHR). Yersinia enterocolitica (Y.e.) has been shown to produce a lipoprotein (LP) that can cross-react with the TSHR and thus can act as a potential trigger of thyroid autoimmunity. In this study, to further characterize LP, we cloned the LP gene from Y. enterocolitica and expressed a recombinant LP. This recombinant LP was mitogenic for C3H/HeJ (LPS hyporesponsive) B cells and induced production and secretion of significant levels of IL-6 from splenocytes. A mouse antibody generated against the recombinant LP cross-reacted with TSHR as shown by western blot analysis. FACS analysis of splenocytes from mice immunized with LP revealed that LP could induce increased expression of B7.1 and B7.2. The immunomodulatory effects of LP including up-regulation of B7.1 and B7.2 coupled with its ability to induce antibodies that can cross-react with the TSHR showed several potential mechanisms by which it can cause breakdown of self-tolerance to TSHR.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 60612, USA.
authors.forename: Eryn
authors.initials: E
authors.lastname: Gangi
authors.forename: Vinayak
authors.initials: V
authors.lastname: Kapatral
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Azami El-Idrissi
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Martinez
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D015850:Interleukin-6 / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D011989:Receptors, Thyrotropin / Q000276:immunology*; D015854:Up-Regulation; D015008:Yersinia enterocolitica / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015850:Interleukin-6; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011989:Receptors, Thyrotropin