title: Tolerogenic function of Blimp-1 in dendritic cells.
abstract: Blimp-1 has been identified as a key regulator of plasma cell differentiation in B cells and effector/memory function in T cells. We demonstrate that Blimp-1 in dendritic cells (DCs) is required to maintain immune tolerance in female but not male mice. Female mice lacking Blimp-1 expression in DCs (DCBlimp-1(ko)) or haploid for Blimp-1 expression exhibit normal DC development but an altered DC function and develop lupus-like autoantibodies. Although DCs have been implicated in the pathogenesis of lupus, a defect in DC function has not previously been shown to initiate the disease process. Blimp-1(ko) DCs display increased production of IL-6 and preferentially induce differentiation of follicular T helper cells (T(FH) cells) in vitro. In vivo, the expansion of T(FH) cells is associated with an enhanced germinal center (GC) response and the development of autoreactivity. These studies demonstrate a critical role for Blimp-1 in the tolerogenic function of DCs and show that a diminished expression of Blimp-1 in DCs can result in aberrant activation of the adaptive immune system with the development of a lupus-like serology in a gender-specific manner. This study is of particular interest because a polymorphism of Blimp-1 associates with SLE.
authors.affiliation: Center for Autoimmune and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yong Rui
authors.initials: YR
authors.lastname: Zou
authors.forename: Jordan
authors.initials: J
authors.lastname: Goldstein
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D015850:Interleukin-6; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1