Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta
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Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta. / Alba, A; Planas, R; Clemente, X; Carrillo, J; Ampudia, R; Puertas, M-C; Pastor, X; Tolosa, E; Pujol-Borrell, R; Verdaguer, J; Vives-Pi, M.
In: CLIN EXP IMMUNOL, Vol. 151, No. 3, 01.03.2008, p. 467-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta
AU - Alba, A
AU - Planas, R
AU - Clemente, X
AU - Carrillo, J
AU - Ampudia, R
AU - Puertas, M-C
AU - Pastor, X
AU - Tolosa, E
AU - Pujol-Borrell, R
AU - Verdaguer, J
AU - Vives-Pi, M
PY - 2008/3/1
Y1 - 2008/3/1
N2 - The destruction of beta cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-beta in beta cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-beta mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-beta transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of beta cell-specific autoimmunity mediated by NK cells.
AB - The destruction of beta cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-beta in beta cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-beta mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-beta transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of beta cell-specific autoimmunity mediated by NK cells.
KW - Animals
KW - B-Lymphocytes
KW - Cytokines
KW - Diabetes Mellitus, Type 1
KW - Disease Models, Animal
KW - Disease Progression
KW - G(M1) Ganglioside
KW - Interferon-beta
KW - Islets of Langerhans
KW - Killer Cells, Natural
KW - Lymph Nodes
KW - Lymphocyte Subsets
KW - Mice
KW - Mice, Inbred NOD
U2 - 10.1111/j.1365-2249.2007.03580.x
DO - 10.1111/j.1365-2249.2007.03580.x
M3 - SCORING: Journal article
C2 - 18190608
VL - 151
SP - 467
EP - 475
JO - CLIN EXP IMMUNOL
JF - CLIN EXP IMMUNOL
SN - 0009-9104
IS - 3
ER -