Immunochemistry

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MHC plays a central role in immune response by presenting peptide antigens to T cells. On the other hand, MHC is strongly associated with susceptibility to autoimmune diseases, allergic diseases, cancer and neurodegenerative diseases. However, it has remained unclear how MHC is involved in the disease susceptibility. We have recently found that MHC class II molecules function like a molecule chaperon to transport cellular misfolded proteins to the cell surface and such proteins are involved in autoimmune diseases as a neo-self that is targeted by autoantibodies. Based on the new findings on MHC, we are studying the mechanism of immune disorders as well as new therapies for immune diseases (Figure 1).

Immune system is a host defense mechanism for pathogens. Therefore, immune system seems to have evolved with pathogens. Immune cells express varieties of receptors that transduce inhibitory and activating signals. Especially, we are studying paired receptors that consist of inhibitory and activating receptors. From our studies on paired receptors, we have elucidated new mechanisms of virus infection (Figure 2), immune evasion by pathogens and host defense to pathogens (Figure 3).

Figure 1

Figure 2

Figure 3

Principal Investigator

Hisashi Arase Professor

Research field: Autoimmunity, Immune regulation, Host pathogen interactions
+81-6-6879-8291
arase atmark biken.osaka-u.ac.jp
Education history

1990.3 Hokkaido University, School of Medicine
1994.3 Hokkaido University, Graduate School of Medicine

Research and career history

1994.4 Research Associate: Department of Molecular Genetics, Center for Neurobiology and Molecular Immunology, School of Medicine, Chiba University, Chiba, Japan
2000.8 Visiting Fellow: University of California San Francisco, San Francisco, CA, USA
2002.8 ssociate Professor: Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan
2004.2 Associate Professor: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
2006.6 Professor: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
2007.10 Professor: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University.

Members

Tadahiro Suenaga Associate Professor
tsue atmark biken.osaka-u.ac.jp
Masako Kohyama Assistant Professor
masakowkt atmark biken.osaka-u.ac.jp
Kouyuki Hirayasu Assistant Professor
hirayasu atmark ifrec.osaka-u.ac.jp
Jin Hui Researcher
huijin atmark biken.osaka-u.ac.jp
 
 

Publication

Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H. LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins. Nat. Microbiol. 1, 1-7, 2016.
Arase, H. Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases Adv. Immunol. 129:1-23, 2015.
Arase, N., Arase, H. Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases. J. Biochem. 158:367-372, 2015.
Kohyama, M., Matsuoka, S., Shida, K., Sugihara, F., Aoshi, T., Kishida, K., Ishii, K.J., Arase, H. Monocyte infiltration into obese and fibrilized tissues is regulated by PILR. Eur. J. Immunol. 46:1214-1223, 2016.
Suenaga, T., Matsumoto, M., Arisawa, F., Kohyama, M., Hirayasu, K., Mori, Y., Arase, H. Sialic acids on varicella-zoster virus glycoprotein B required for cell-cell fusion J. Biol. Chem. 290:19833-19843, 2015.
Tanimura, K., Jin, H, Suenaga, T., Morikami, S., Arase, N., Kishida, K., Hirayasu, K., Kohyama, M., Ebina, Y., Yasuda, S., Horita, T., Takasugi, K., Ohmura, K., Yamamoto, K., Katayama, I., Sasazuki, T., Lanier. L. L., Atsumi, T., Yamada, H. and Arase, H. β2-glycoprotein I / HLA class II complexes are novel autoantigens in antiphospholipid syndrome. Blood. 125, 2835-2844, 2015.
Hirayasu, K., Arase, H. Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations. J. Hum. Genet. 60:703-708, 2015.
Jin, H., Arase, N., Hirayasu, K., Kohyama, M., Suenaga, T., Saito, F., Tanimura, K., Matsuoka, S., Ebina, K., Shi, K., Toyama-Sorimachi, N., Yasuda, S., Horita, T., Hiwa, R., Takasugi, K., Ohmura, K., Yoshikawa, H., Saito, T., Atsumi, T., Sasazuki, T., Katayama, I., L. Lanier, L., and Arase, H. Autoantibodies to IgG/HLA-DR complexes are associated with rheumatoid arthritis susceptibility. Proc. Natl. Acad. Sci. USA. 111, 3787-3792, 2014.
Kuroki, K., Wang, J., Ose, T., Yamaguchi, M., Tabata, S., Maita, N., Nakamura, S., Kajikawa, M., Kogure, A., Satoh, T., Arase, H. and Maenaka, K. Structural basis for simultaneous recognition of an O-glycan and its attached peptide of mucin family by immune receptor PILRα. Proc. Natl. Acad. Sci. USA. 111:8877-8882. 2014
Wang, J., Arase, H. Regulation of immune responses by neutrophils. Ann. N. Y. Acad. Sci. 1319:66-81, 2014.
Wang, J., Shiratori, I., Uehori, J., Ikawa, M., Arase, H. Neutrophil infiltration during inflammation is regulated by PILRα via modulation of integrin activation. Nat. Immunol. 14, 34-40, 2012.
Jiang, Y., Arase, N., Kohyama, M., Hirayasu, K., Suenaga, T., Jin, H., Matsumoto, M., Shida, K., L. Lanier, L., Saito, T. and Arase, H. Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. Int. Immunol. 25:235-246, 2013.
Tanaka, Y., Suenaga, T., Matsumoto, M., Seya, T., Arase, H. Herpesvirus 6 Glycoproteins B (gB), gH, gL and gQ are Necessary and Sufficient for Cell-to-Cell Fusion. J. Virol. 87:10900-10903, 2013.
Hirayasu, K., Ohashi, J., Kashiwase, K., Hananantachai, H., Naka, I., Ogawa, A., Takanashi, M., Satake, M., Nakajima, K., Parham, P., Arase, H., Tokunaga, K., Patarapotikul, J., Yabe, T. Significant Association of KIR2DL3-HLA-C1 Combination with Cerebral Malaria and Implications for Co-evolution of KIR and HLA. PLoS Pathog. 8:e1002565, 2012.
Kogure, A., Shiratori, I., Wang, J., L. Lanier, L.,Arase, H. PANP is a novel O-glycosylated PILR ligand expressed in neural tissues. Biochem Biophys Res Commun 405:428-433, 2011.
Suenaga, T., Satoh, T., Somboonthum, P., Kawaguchi, Y., Mori, Y., and Arase, H. Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. Proc. Natl. Acad. Sci. USA 107:866-871, 2010.
Arii, J., Goto, H., Suenaga, T., Oyama, M., Kozika-Hata, H., Imai, T., Minowa, A., Akashi, H., Arase, H., Kawaoka, Y., and Kawaguchi, Y.. Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1. Nature 467:859-862, 2010
Wang, J., Fan, Q., Satoh, T., Arii, J., Lanier, L.L., Spear, P.G., Kawaguchi, Y., Arase, H. Binding of herpes simplex virus glycoprotein B (gB) to PILRα depends on specific sialylated O-linked glycans on gB J. Virol.83:13042-13045, 2009.
Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P.G., Lanier, L.L. and Arase, H. PILRα is a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B. Cell 132:935-944, 2008.
Wang, J., Shiratori, I., Satoh, T., Lanier, L.L., and Arase, H. An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired immunoglobulin-like type 2 receptor (PILR). J. Immunol.180:1686-1693, 2008.

Prize

2013 The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology: Prizes for Science and Technology (Research Category)
2011 The 14th Japanese Society for Immunology Award