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Int J Clin Exp Pathol 2010;3(1):24-38
Review Article
HMGB1, an innate alarmin, in the pathogenesis of type 1 diabetes
Shu Zhang, Jixin Zhong, Ping Yang, Feili Gong, Cong-Yi Wang
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Hua-Zhong University of Science and Technology, 1095 Jiefang
Ave., Wuhan, 430030, China; The Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098,
Augusta, GA 30912, USA; Department of Immunology, Tongji Medical College, Hua-Zhong University of Science and Technology, 13 Hong
Kong Road, Wuhan, 430030, China; Georgia Esoteric & Molecular laboratories, Department of Pathology, Medical College of Georgia, 1120
15th Street, Augusta, GA 30912, USA
Received July 21, 2009; accepted August 5, 2009; Available online September 8, 2009
Abstract: HMGB1, an evolutionarily conserved chromosomal protein, was recently re-discovered to act as a “danger signal” (alarmin) to alert
the innate immune system for the initiation of host defense or tissue repair. Extracellular HMGB1 can be either passively released from
damaged/necrotic cells or secreted by activated immune cells. Upon stimulation, dendritic cells (DCs), macrophages and natural killer (NK)
cells secrete high levels of HMGB1 into the intercellular milieu. HMGB1 is potent to target DCs, macrophages, neutrophils and CD4+ T cells. It
also upregulates the expression of BCL-XL by which it may prevent the elimination of activated immune cells. As a result, HMGB1 has been
suggested to be implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis
(RA), and experimental allergic encephalomyelitis (EAE). Given the similarities of autoimmune response against beta cell self-antigens in type
1 diabetes (T1D), in this view we will discuss the possible implications of HMGB1 in T1D pathogenesis. Specifically, we will summarize and
update the advancement of HMGB1 in the pathogenesis of autoimmune initiation and progression during T1D development, as well as islet
allograft rejection of diabetic patients after islet transplantation. Elucidation of the role for HMGB1 in T1D pathogenesis would not only enhance
the understanding of disease etiology, but also have the potential to shed new insight into the development of therapeutic strategies for
prevention or intervention of this disorder. (IJCEP907007).
Key words: HMGB1, innate alarmin, pathogenesis type 1 diabetes, review
Full text PDF
Address all correspondence to:
Cong-Yi Wang, MD
The Center for Biotechnology and Genomic Medicine
Medical College of Georgia
1120 15th street, CA4098
Augusta, GA 30912
USA.
E-mail: cwang@mcg.edu
Review Article
HMGB1, an innate alarmin, in the pathogenesis of type 1 diabetes
Shu Zhang, Jixin Zhong, Ping Yang, Feili Gong, Cong-Yi Wang
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Hua-Zhong University of Science and Technology, 1095 Jiefang
Ave., Wuhan, 430030, China; The Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098,
Augusta, GA 30912, USA; Department of Immunology, Tongji Medical College, Hua-Zhong University of Science and Technology, 13 Hong
Kong Road, Wuhan, 430030, China; Georgia Esoteric & Molecular laboratories, Department of Pathology, Medical College of Georgia, 1120
15th Street, Augusta, GA 30912, USA
Received July 21, 2009; accepted August 5, 2009; Available online September 8, 2009
Abstract: HMGB1, an evolutionarily conserved chromosomal protein, was recently re-discovered to act as a “danger signal” (alarmin) to alert
the innate immune system for the initiation of host defense or tissue repair. Extracellular HMGB1 can be either passively released from
damaged/necrotic cells or secreted by activated immune cells. Upon stimulation, dendritic cells (DCs), macrophages and natural killer (NK)
cells secrete high levels of HMGB1 into the intercellular milieu. HMGB1 is potent to target DCs, macrophages, neutrophils and CD4+ T cells. It
also upregulates the expression of BCL-XL by which it may prevent the elimination of activated immune cells. As a result, HMGB1 has been
suggested to be implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis
(RA), and experimental allergic encephalomyelitis (EAE). Given the similarities of autoimmune response against beta cell self-antigens in type
1 diabetes (T1D), in this view we will discuss the possible implications of HMGB1 in T1D pathogenesis. Specifically, we will summarize and
update the advancement of HMGB1 in the pathogenesis of autoimmune initiation and progression during T1D development, as well as islet
allograft rejection of diabetic patients after islet transplantation. Elucidation of the role for HMGB1 in T1D pathogenesis would not only enhance
the understanding of disease etiology, but also have the potential to shed new insight into the development of therapeutic strategies for
prevention or intervention of this disorder. (IJCEP907007).
Key words: HMGB1, innate alarmin, pathogenesis type 1 diabetes, review
Full text PDF
Address all correspondence to:
Cong-Yi Wang, MD
The Center for Biotechnology and Genomic Medicine
Medical College of Georgia
1120 15th street, CA4098
Augusta, GA 30912
USA.
E-mail: cwang@mcg.edu
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