title: CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis.
abstract: Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag(-/-) mice. The CD8α(+) DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4(+) T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4(+) T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α(+) DCs and other cells of the immune system.
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Qi-Quan
authors.initials: QQ
authors.lastname: Huang
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Birkett
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Renee
authors.identifier: 0000000310196783
authors.initials: R
authors.lastname: Doyle
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Pathology, Mount Sinai Hospital School of Medicine, New York city, New York 10029, USA.
authors.forename: G Kenneth
authors.initials: GK
authors.lastname: Haines
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, VA Health Care System, Palo Alto, California 94304, USA.
authors.forename: William
authors.initials: W
authors.lastname: Robinson
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Syamal
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Biochemistry, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Phee
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pope
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies; D001327:Autoimmune Diseases; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes; D003713:Dendritic Cells; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory
chemical_list: D001323:Autoantibodies; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D039521:CD11c Antigen