Toll-like receptor homolog RP105 modulates the antigen-presenting cell function and regulates the development of collagen-induced arthritis.
BACKGROUND
RP105 is a Toll-like receptor homolog expressed on B cells, dendritic cells (DCs), and macrophages. We investigated the role of RP105 in the development of collagen-induced arthritis (CIA).


METHODS
CIA was induced in RP105-deficient DBA/1 mice and the incidence and arthritis index were analyzed. The cytokine production by spleen cells was determined. The functions of the DCs and regulatory T cells (Tregs) from RP105-deficient or control mice were determined by adding these cells to the lymph node cell culture. Arthritis was also induced by incomplete Freund's adjuvant (IFA) plus collagen or by injecting anti-collagen antibody and lipopolysaccharide.


RESULTS
RP105-deficient mice showed accelerated onset of arthritis and increased severity. Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha production by spleen cells from RP105-deficient mice was increased in comparison with that from wild-type mice. The DCs from RP105-deficient mice induced more IFN-gamma production, whereas Tregs from those mice showed less inhibitory effect against IFN-gamma production. RP105-deficient mice also showed more severe arthritis induced by collagen with IFA.


CONCLUSIONS
These results indicate that RP105 regulates the antigen-presenting cell function and Treg development, which induced the attenuation of the cell-mediated immune responses and, as a result, suppressed the development of CIA.
Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. taday@cc.saga-u.ac.jp
Yoshifumi
Y
Tada
Syuichi
S
Koarada
Fumitaka
F
Morito
Mio
M
Mitamura
Hisako
H
Inoue
Rie
R
Suematsu
Akihide
A
Ohta
Kensuke
K
Miyake
Kohei
K
Nagasawa
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D015703:Antigens, CD; C490500:Ly78 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma