Trends in Immunology
ReviewAutoimmunity and the environmentInduction of autoimmunity by pristane and other naturally occurring hydrocarbons
Section snippets
The immunological effects of TMPD (pristane]
The naturally occurring hydrocarbon oil TMPD (2,6,10,14-tetramethylpentadecane), more commonly known as pristane, induces chronic inflammation when introduced into the peritoneal cavity. Over the past 15 years, it has been found that the inflammatory response to TMPD causes a lupus-like disease in mice. The mechanisms involved in TMPD-lupus are coming into clearer focus and may be highly relevant to human systemic lupus erythematosus (SLE), an immune disorder increasingly linked to the
Autoantibodies in TMPD-treated mice
Consistent with the evidence that exposure to adjuvant hydrocarbons may provoke inflammatory or autoimmune responses in humans, BALB/c mice injected intraperitoneally (i.p.) with TMPD develop a local inflammatory response (lipogranulomas) and an erosive arthritis resembling rheumatoid arthritis (RA) [18] and TMPD was subsequently found to induce autoantibodies and the clinical manifestations of SLE [19].
Susceptibility to TMPD-lupus among non-autoimmune prone mice is widespread [20]. The
Autoimmune disease in TMPD-treated mice
TMPD treated mice develop clinical manifestations of lupus, including arthritis, immune complex-mediated glomerulonephritis, and pulmonary capillaritis as well as autoantibodies. Inflammation of the pericardium and pleura also occurs, but it is unclear whether this is autoimmune in origin. SLE is a human syndrome classified using a set of 11 criteria and TMPD-treated mice meet these criteria (Table 2). As in TMPD lupus [36], human SLE is primarily a disease of females (female: male ratio ∼9:1).
The role of Type I interferon (IFN-I) in SLE
IFN-I is increasingly recognized as a key mediator of SLE. The IFN-I family includes multiple IFNα subtypes and IFNβ, all binding the same IFNAR (receptor) complex [49]. Initially described for its anti-viral effects, IFN-I links innate and adaptive immunity. Details of IFN-I biology and functions have been reviewed [49] and will not be discussed further. Elevated serum IFN-I was noted in SLE patients 30 years ago [50] and interest in the antiviral cytokine family has revived with recognition
Association of lymphoid neogenesis with autoimmunity
Although originally termed “lipogranulomas”, the inflammatory lesions arising in response to the presence of TMPD within the peritoneal cavity actually represent a striking example of lymphoid neogenesis [60]. Lymphoid neogenesis, the formation of ectopic lymphoid tissue at sites of inflammation [81], is strongly associated with autoantibody production [82]. Ectopic lymphoid tissue closely resembles secondary lymphoid tissue and arises by a similar developmental pathway. It frequently exhibits
Summary and conclusions
TMPD-lupus is a model of SLE associated with IFN-I dysregulation. The pathogenesis of lupus autoantibodies and glomerulonephritis in this model strictly requires IFNAR signaling. Most of the IFN-I is produced by immature monocytes instead of PDCs, and its production is mediated exclusively by the TLR7-MyD88 pathway. It is likely that endogenous TLR7 ligands such as U1RNA are involved, as germ-free mice are susceptible to disease induction. However, immune complex uptake via Fc receptors is
Acknowledgements
This work was supported by research grants AR44731 and AR51766 from the US Public Health Service and by the Lupus Foundation of America. P.Y.L and J.S.W are NIH T32 trainees (DK07518 and AR007603).
Glossary
- ANA
- antinuclear antibodies
- AFC
- antibody forming cell
- dsDNA
- double-stranded DNA
- FcγR
- Fcγ receptor
- IFN
- interferon
- IFN-I
- type-I interferons
- IFNAR
- Interferon alpha/beta receptor
- i.p.
- intraperitoneal
- IPS-1
- interferon-β promoter stimulator-1
- ISG
- Interferon stimulated gene
- MCP
- monocyte chemoattractant protein
- MyD88
- myeloid differentiation factor 88
- NZB/W
- (New Zealand Black X New Zealand White) F1 hybrid mice
- NP-KLH
- 4-hydroxy-3-nitrophenyl acetyl-conjugated keyhole limpet hemocyanin
- OVA
- ovalbumin
- PECs
- peritoneal exudate cells
- PDCs
References (93)
- et al.
On the origin of pristane in marine organisms
J. Lipid Res.
(1968) Dietary exposures to mineral hydrocarbons from food-use applications in the United States
Food Chem. Toxicol.
(2002)Follicular (mineral oil) lipidosis: I. Epidemiologic studies of involvement of the spleen
Hum. Pathol
(1984)- et al.
Mineral oil (follicular) lipidosis: II. histologic studies of spleen, liver, lymph nodes, and bone marrow
Hum. Pathol
(1984) Induction of lupus autoantibodies by adjuvants
J. Autoimm.
(2003)Pristane-induced autoimmunity in germ-free mice
Clin. Immunol.
(2005)Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice
Toxicology
(2006)A female preponderance for chemically induced lupus in SJL/J mice
Clin. Immunol.
(2007)Interferon-gamma promotes lupus nephritis in mice treated with the hydrocarbon oil pristane
Kidney Int.
(2001)Nephritogenic autoantibodies but absence of nephritis in IL-12p35-deficient mice with pristane-induced lupus
Kidney Int.
(2003)
Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus
Clin. Immunol.
Type I interferon in systemic lupus erythematosus and other autoimmune diseases
Immunity
Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14 tetramethylpentadecane (pristane)
Am. J. Pathol
U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7
Blood
Autoantibody synthesis in salivary glands of Sjogren's syndrome patients
J. Autoimmun.
Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6
Immunity
Mineral oil material in canned foods
Food Additives & Contaminants
Migration of mineral hydrocarbons into foods. 4. Waxed paper for packaging dry goods including bread, confectionary and for domestic use including microwave cooking
Food Additives and Contaminants
Mineral oil lipogranulomata in liver and spleen: a study of 465 autopsies
Arch. Pathol. Lab. Med.
Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants
Nature (Lond.)
Induction of plasma cell tumours in BALB/c mice with 2,6,10,14-tetramethylpentadecane (pristane)
Nature (Lond.)
Plasmacytomagenesis in mice: model of neoplastic development dependent upon chromosomal translocations
Carcinogenesis
Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition
Immunology
Hand injuries due to high-pressure injection devices for painting in shipyards: circumstances, management, and outcome in twelve patients
Am. J. Ind. Med.
Exogenous lipoid pneumonia
Arch. Intern. Med.
Lipogranulomas in non-fatty human livers: a mineral oil induced environmental disease
Am. J. Clin. Pathol.
Association between occupational exposure to mineral oil and rheumatoid arthritis: results from the Swedish EIRA case-control study
Arthritis Res. Ther.
Cluster of systemic lupus erythematosus (SLE) associated with an oil field waste site: a cross sectional study
Environ. Health
Vaccination-induced systemic autoimmunity in farmed Atlantic salmon
J. Immunol.
Genetics of susceptibility to pristane-induced plasmacytomas in BALB/cAn: Reduced susceptibility in BALB/cJ with a brief description of pristane-induced arthritis
J. Immunol.
Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane
J. Exp. Med.
Widespread susceptibility among inbred mouse strains to the induction of lupus autoantibodies by pristane
Clin. Exp. Immunol.
Pristane-induced arthritis. The immunologic and genetic features of an experimental murine model of autoimmune disease
Arthritis Rheum.
Antinuclear antibody production and immune complex glomerulonephritis in BALB/c mice treated with pristane
Proc. Natl. Acad. Sci. USA
Distinctive patterns of autoimmune response induced by different types of mineral oil
Toxicol. Sci.
Tolerance to self antigens in normal and lupus mice: the role of autoantigen specific B and T cell responses in autoantibody production
Rheumatology in Europe Supplement
Autoimmune targeting of key components of RNA interference
Arthritis Res. Ther.
Disparate T cell requirements of two subsets of lupus-specific autoantibodies in pristane-treated mice
Clin. Exp. Immunol.
Pristane induced arthritis in mice. IV. Immunotherapy with monoclonal antibodies directed against lymphocyte subsets
J. Rheumatol
IL–6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus
J. Exp. Med
Deficiency of the Type I interferon receptor protects mice from experimental lupus
Arthritis Rheum.
Cross talk of the interferon-alpha/beta signalling complex with gp130 for effective interleukin-6 signalling
Genes Cells
Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3
EMBO J
Anti-tumour necrosis factor therapy ameliorates joint disease in a chronic model of inflammatory arthritis
Br. J. Rheumatol.
Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane
J. Immunol.
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