2001 Fiscal Year Final Research Report Summary
Development of Autoimmune Disease Models Based on FcyRIIB-Deficient Mice
| Project/Area Number |
12557014
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
TAKAI Toshiyuki Institute of Development, Aging and Cancer, Tohoku University, Professor, 加齢医学研究所, 教授 (20187917)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Autoimmunity / Allergy / FcγRIIB / Gene Targeting / Model construction_ / PIR |
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| Research Abstract |
The receptors for Fc protion of immunoglobulins, Fc receptors (FcRs), combine innate and adaptive immunity and are critical elements to activate or down-modulate the immune responses. Activity of various cells in the immune system is intimately regulated by the balanced signaling through FcRs. Development of many autoimmune diseases in humans may now be interpreted by the impairement in the FcR regulatory system. To address the question whether the type IIB Fc receptor for IgG (FcγRIIB)-deficient mice (RIIB-/-) are susceptible to induction of various autoimmune diseases, we tested to induce type II collagen-induced arthritis (CIA), a model for rheumatoid arthritis in humans. We found that RIIB-/- on a non-permissive H-2b background become susceptible to CIA induction. Moreover, we could induce Goodpasture' s syndrome (GPS) in RIIB-/- by immunization with type IV collagen. Quite similar to human GPS, RIIB-/- develop massive pulmonary hemorrhage and glomerulonephritis. These results highlight the role of FcγRIIB in maintaining tolerance and suggest that it may play a critical role in the pathogenesis of rheumatoid arthritis and GPS in humans.
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[Publications] Kubo, S., Matsuoka, K., Taya, C., Kitamura, F., Takai, T., Yonekawa, H., Karasuyama, H.: "Drastic up-regulation of FcεRI on mast cells is induced by IgE binding through stabilization and accumulation of FcεRI on the cell surface"J. Immunol.. 167 (6). 3427-3434 (2001)
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[Publications] Yoneto, T., Waki, S., Takai, T., Tagawa, Y., Iwakura, Y., Mizuguchi, J., Nariuchi, H., and Yoshimoto, T.: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infaction"J. Immunol.. 166 (10). 6236-6241 (2001)
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[Publications] Lee, K.H., Ono, M., Inui, M., Yuasa, T., and Takai, T.: "(2000) Stimulatory function of gp49A, a murine Ig-like receptor, in RBL-2H3 cells"J. Immunol.. 165 (9). 4970-4977 (2001)
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[Publications] Wakayama, H., Hasegawa, Y., Kawabe, T., Hara, T., Matsuo, S., Mizuno, M., Takai,T., Kikutani, H., Shimokata, K.: "Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice"Eur. J. Immunol.. 30 (4). 1182-1190 (2000)
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[Publications] Schiller, C., Janssen-Graalfs, I., Baumann, U., Schwerter-Strumpf, K., Izui, S., Takai, T., Schmidt, R.E., and Gessner, J.E.: "Mouse FcγRII is a negative regulator of FcγRIII in IgG immune complex triggered inflammation but not in antoantibody induced hemolysis"Eur. J. Immunol.. 30. 481-490 (2000)
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[Publications] Nakamura, A., Yuasa, T., Ujike, A., Ono, M., Nukiwa, T., Ravetch, J.V., Takai , T.: "Fcγ receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease"J. Exp. Med.. 191 (5). 899-906 (2000)
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[Publications] Cortegano, I., del Pozo, V., Cardaba, B., Arrieta, I., Gallardo, S., Rojo, M., Aceituno, E., Takai, T., Verbeek, S., Palomino, P., Liu, F.T., and Lahoz, C.: "Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene: Implication of the promoter sequence IL-5REIII."Glycobiol.. 10 (3). 237-242 (2000)
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