title: Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage.
abstract: Dendritic cells (DCs) initiate and control the adaptive immune response against infections. However, their contributions to the anti-self adaptive immune response in autoimmune disorders like systemic lupus erythematosus are uncertain. By constitutively deleting DCs in MRL.Fas(lpr) mice, we show that they have complex roles in murine lupus. The net effect of DC deletion was to ameliorate disease. DCs were crucial for the expansion and differentiation of T cells but, surprisingly, not required for their initial activation. Correspondingly, kidney interstitial infiltrates developed in the absence of DCs, but failed to progress. DC deletion concomitantly decreased inflammatory and regulatory T cell numbers. Unexpectedly, plasmablast numbers and autoantibody concentrations depended on DCs, in contrast to total serum immunoglobulin concentrations, suggesting an effect of DCs on extrafollicular humoral responses. These findings reveal that DCs operate in unanticipated ways in murine lupus and validate them as a potential therapeutic target in autoimmunity.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Lino L
authors.initials: LL
authors.lastname: Teichmann
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Ols
authors.forename: Michael
authors.initials: M
authors.lastname: Kashgarian
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001781:Blood Component Removal; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D017578:Immunoglobulin Class Switching; D007371:Interferon-gamma / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D007371:Interferon-gamma