Enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXCR3 circuit: a mechanism of accelerated beta-cell failure in fulminant type 1 diabetes.
Enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXCR3 circuit: a mechanism of accelerated beta-cell failure in fulminant type 1 diabetes.
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DOI：
10.2337/db09-0091
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发表时间：
2009-10
期刊：
影响因子：
7.7
通讯作者：
Kobayashi T
中科院分区：
文献类型：
--
作者：
Tanaka S;Nishida Y;Aida K;Maruyama T;Shimada A;Suzuki M;Shimura H;Takizawa S;Takahashi M;Akiyama D;Arai-Yamashita S;Furuya F;Kawaguchi A;Kaneshige M;Katoh R;Endo T;Kobayashi T
Fulminant type 1 diabetes is characterized by the rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetes complications. Causative mechanisms for accelerated β-cell failure are unclear. Subjects comprised three autopsied patients who died from diabetic ketoacidosis within 2–5 days after onset of fulminant type 1 diabetes. We examined islet cell status, including the presence of enterovirus and chemokine/cytokine/major histocompatibility complex (MHC) expressions in the pancreata using immunohistochemical analyses and RT-PCR. Immunohistochemical analysis revealed the presence of enterovirus-capsid protein in all three affected pancreata. Extensive infiltration of CXCR3 receptor–bearing T-cells and macrophages into islets was observed. Dendritic cells were stained in and around the islets. Specifically, interferon-γ and CXC chemokine ligand 10 (CXCL10) were strongly coexpressed in all subtypes of islet cells, including β-cells and α-cells. No CXCL10 was expressed in exocrine pancreas. Serum levels of CXCL10 were increased. Expression of MHC class II and hyperexpression of MHC class I was observed in some islet cells. These results strongly suggest the presence of a circuit for the destruction of β-cells in fulminant type 1 diabetes. Enterovirus infection of the pancreas initiates coexpression of interferon-γ and CXCL10 in β-cells. CXCL10 secreted from β-cells activates and attracts autoreactive T-cells and macrophages to the islets via CXCR3. These infiltrating autoreactive T-cells and macrophages release inflammatory cytokines including interferon-γ in the islets, not only damaging β-cells but also accelerating CXCL10 generation in residual β-cells and thus further activating cell-mediated autoimmunity until all β-cells have been destroyed.
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DOI：
10.4049/jimmunol.0803543
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Melli K;Friedman RS;Martin AE;Finger EB;Miao G;Szot GL;Krummel MF;Tang Q
通讯作者：
Tang Q
DOI：
10.1196/annals.1288.059
发表时间：
2003-01-01
期刊：
IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN
影响因子：
--
作者：
Nakagawa, Y;Shimada, A;Saruta, T
通讯作者：
Saruta, T
影响因子：
4.4
作者：
Christen, U;McGavern, DB;Oldstone, MBA
通讯作者：
Oldstone, MBA
影响因子：
8.2
作者：
FOULIS, AK;FARQUHARSON, MA;KANDOLF, R
通讯作者：
KANDOLF, R
影响因子：
82.9
作者：
Lang, KS;Recher, M;Zinkernagel, RM
通讯作者：
Zinkernagel, RM