Type 1 diabetes: translating mechanistic observations into effective clinical outcomes

被引:184
作者
Herold, Kevan C. [1 ]
Vignali, Dario A. A. [2 ]
Cooke, Anne [3 ]
Bluestone, Jeffrey A. [4 ,5 ]
机构
[1] Yale Univ, Dept Immunobiol, New Haven, CT 06520 USA
[2] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[3] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[4] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
基金
美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;
关键词
BETA-CELL FUNCTION; CD8(+) T-CELLS; ANTI-CD3; MONOCLONAL-ANTIBODY; GROWTH-FACTOR-BETA; RECENT-ONSET; DOUBLE-BLIND; NOD MICE; TGF-BETA; B-CELLS; C-PEPTIDE;
D O I
10.1038/nri3422
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Type 1 diabetes (T1D) remains an important health problem, particularly in western countries, where the incidence has been increasing in younger children. In 1986, Eisenbarth described T1D as a chronic autoimmune disease. Work over the past three-and-a-half decades has identified many of the genetic, immunological and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis. Clinical trials have been conducted to test these hypotheses but have had mixed results. Here, we discuss the findings that have led to our current concepts of the disease mechanisms involved in T1D and the clinical studies promoted by these studies. The findings from preclinical and clinical studies support the original proposed model for how T1D develops but have also suggested that this disease is more complex than was originally thought and will require broader treatment approaches.
引用
收藏
页码:243 / 256
页数:14
相关论文
共 180 条
[41]   Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients [J].
Dotta, Francesco ;
Censini, Stefano ;
van Halteren, Astrid G. S. ;
Marselli, Lorella ;
Masini, Matilde ;
Dionisi, Sabrina ;
Mosca, Franco ;
Boggi, Ugo ;
Muda, Andrea Onetti ;
Del Prato, Stefano ;
Elliott, John F. ;
Covacci, Antonello ;
Rappuoli, Rino ;
Roep, Bart O. ;
Marchetti, Piero .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (12) :5115-5120
[42]   Opinion - A worm's eye view of the immune system: consequences for evolution of human autoimmune disease [J].
Dunne, DW ;
Cooke, A .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (05) :420-426
[43]  
EISENBARTH GS, 1986, NEW ENGL J MED, V314, P1360
[44]  
EISENBARTH GS, 1985, DIABETES RES CLIN EX, V2, P271
[45]   β-cell apoptosis and defense mechanisms -: Lessons from type 1 diabetes [J].
Eizirik, DL ;
Darville, MI .
DIABETES, 2001, 50 :S64-S69
[46]   Control of TH17 cells occurs in the small intestine [J].
Esplugues, Enric ;
Huber, Samuel ;
Gagliani, Nicola ;
Hauser, Anja E. ;
Town, Terrence ;
Wan, Yisong Y. ;
O'Connor, William, Jr. ;
Rongvaux, Anthony ;
Van Rooijen, Nico ;
Haberman, Ann M. ;
Iwakura, Yoichiro ;
Kuchroo, Vijay K. ;
Kolls, Jay K. ;
Bluestone, Jeffrey A. ;
Herold, Kevan C. ;
Flavell, Richard A. .
NATURE, 2011, 475 (7357) :514-U114
[47]   B-CELL FUNCTION AND BLOOD-GLUCOSE CONTROL IN INSULIN DEPENDENT DIABETICS WITHIN FIRST MONTH OF INSULIN-TREATMENT [J].
FABER, OK ;
BINDER, C .
DIABETOLOGIA, 1977, 13 (03) :263-268
[48]   Defining the role of the MHC in autoimmunity: A review and pooled analysis [J].
Fernando, Michelle M. A. ;
Stevens, Christine R. ;
Walsh, Emily C. ;
De Jager, Philip L. ;
Goyette, Philippe ;
Plenge, Robert M. ;
Vyse, Timothy J. ;
Rioux, John D. .
PLOS GENETICS, 2008, 4 (04)
[49]   Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes [J].
Fiorina, Paolo ;
Vergani, Andrea ;
Dada, Shirine ;
Jurewicz, Mollie ;
Wong, Masie ;
Law, Kenneth ;
Wu, Erxi ;
Tian, Ze ;
Abdi, Reza ;
Guleria, Indira ;
Rodig, Scott ;
Danussi-Joannopoulos, Kyri ;
Bluestone, Jeff-Rey ;
Sayegh, Mohamed H. .
DIABETES, 2008, 57 (11) :3013-3024
[50]   INSULITIS IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS IN MAN - MACROPHAGES, LYMPHOCYTES, AND INTERFERON-GAMMA CONTAINING CELLS [J].
FOULIS, AK ;
MCGILL, M ;
FARQUHARSON, MA .
JOURNAL OF PATHOLOGY, 1991, 165 (02) :97-103