title: Increased CD1c+ mDC1 with mature phenotype regulated by TNFα-p38 MAPK in autoimmune ocular inflammatory disease.
abstract: In this study we investigated the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c(+) mDC1 in uveitis patients. The increased CD1c(+) mDC1 exhibited high HLADR expression and less antigen uptake. CD1c(+) mDC1 were divided into two subpopulations. CD1c(hi) mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1c(lo) mDC1 subpopulation. Importantly, the CD1c(hi) mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD4(+)CD62L(-) T helper cell proliferation. The mature phenotype and function of CD1c(+) mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c(+) mDC1.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Ophthalmology Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHSFT, Edgbaston, Birmingham B15 2WB, UK; Centre for Translational Inflammation Research, University of Birmingham, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Denniston
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hannes
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: William
authors.initials: W
authors.lastname: Tucker
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Baoying
authors.initials: B
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tiaojiang
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sima
authors.initials: S
authors.lastname: Hirani
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shayma
authors.initials: S
authors.lastname: Jawad
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Si
authors.affiliation: Department of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Richard W J
authors.initials: RW
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: nussenblattr@nei.nih.gov.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Antigen uptake; Autoimmune uveitis; CD1c(+) mDC1; CD1c(hi) mDC1 subpopulation; TNFα; p38 MAPK