Th17 development and autoimmune arthritis in the absence of reactive oxygen species

• Dendritic cells (DC) express a functional NADPH oxidase and produce reactive oxygen species (ROS) upon interaction with microbes and T cells. Exposure to ROS leads to DC activation and maturation, as evidenced by phenotypic and functional changes. We have evaluated how endogenous ROS production affects the cytokine secretion pattern and T cell-activating capacity of bone marrow-derived murine DC. DC treated with ROS scavengers, as well as DC from mice that lack a functional NADPH oxidase (and thereby inherently deficient in ROS production) produced significantly increased levels of IL-1β, IL-6, TNF-α and TGF-β in response to microbial activation. DC deficient in ROS production induced high levels of IFN-γ and IL-17 in responding T cells after Ag-specific or superantigen-induced activation. Finally, we show that ROS deficiency affected the induction of a T cell-dependent inflammatory condition, collagen-induced arthritis (CIA). C57BL/6 mice that lack a functional NADPH oxidase developed a severe and erosive CD4-dependent CIA, whereas the majority of the congenic wild-type animals remained healthy. These data suggest that ROS act as immunomodulators in DC-driven T cell activation and perhaps also in T cell-dependent immunopathology. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

CD4+ T cells

Cytokines

Dendritic cells

Immune regulation

Rheumatology

interleukin 1beta

reactive oxygen metabolite

reduced nicotinamide adenine dinucleotide phosphate dehydrogenase

transforming growth factor beta

tumor necrosis factor alpha

collagen type 2

gamma interferon

interleukin 17

reduced nicotinamide adenine dinucleotide phosphate oxidase

animal cell

animal experiment

animal tissue

antibody production

arthritis

article

autoimmune disease

CD4+ T lymphocyte

cell activation

cell maturation

cell strain

controlled study

cytokine release

dendritic cell

helper cell

immune response

immunomodulation

immunopathogenesis

male

mouse

nonhuman

priority journal

protein function

T lymphocyte activation

th17 cell

animal

biosynthesis

C57BL mouse

chronic granulomatous disease

genetics

immunology

metabolism

mouse mutant

phenotype

Animals

Autoimmune Diseases

Collagen Type II

Granulomatous Disease

Chronic

Interferon Type II

Interleukin-17

Mice

Mice

Inbred C57BL

Mice

Knockout

NADPH Oxidase

Reactive Oxygen Species

T-Lymphocytes

Helper-Inducer

Animals

Arthritis

metabolism

Autoimmune Diseases

immunology

Collagen Type II

Dendritic Cells

Granulomatous Disease

Chronic

Interferon Type II

biosynthesis

Interleukin-17

Male

Mice

Inbred C57BL

Knockout

NADPH Oxidase

deficiency

genetics

Phenotype

Reactive Oxygen Species

T-Lymphocytes

Helper-Inducer

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)