Publikationsdatum:
2014-10-18
Beschreibung:
T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Yoshinaga -- Hashimoto, Motomu -- Hirota, Keiji -- Ohkura, Naganari -- Morikawa, Hiromasa -- Nishikawa, Hiroyoshi -- Tanaka, Atsushi -- Furu, Moritoshi -- Ito, Hiromu -- Fujii, Takao -- Nomura, Takashi -- Yamazaki, Sayuri -- Morita, Akimichi -- Vignali, Dario A A -- Kappler, John W -- Matsuda, Shuichi -- Mimori, Tsuneyo -- Sakaguchi, Noriko -- Sakaguchi, Shimon -- R01 DK089125/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):363-8. doi: 10.1126/science.1259077.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. ; Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. ; Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of Frontier Research in Tumor Immunology, Center of Medical Innovation and Translational Research, Osaka University, Osaka 565-0871, Japan. ; Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Department of Geriatric and Environmental Dermatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. ; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. ; Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA. Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206, USA. ; Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan. shimon@ifrec.osaka-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324392" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Arthritis, Rheumatoid/genetics/*immunology
;
Autoantigens/*immunology
;
Autoimmunity/*immunology
;
DNA-Binding Proteins/genetics
;
Gene Expression Regulation
;
Genes, T-Cell Receptor beta
;
Humans
;
Mice
;
Mice, Inbred BALB C
;
Mice, Mutant Strains
;
Receptors, Antigen, T-Cell/*immunology
;
Ribosomal Proteins/genetics/*immunology
;
T-Lymphocytes/*immunology
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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