详细记录  
题名:Soluble factors secreted by T cells promote beta-cell proliferation.
作者:DIRICE E; KAHRAMAN S; JIANG W; EL OUAAMARI A; DE JESUS DF; TEO AK; HU J; KAWAMORI D; GAGLIA JL; MATHIS D; KULKARNI RN;
来源:Diabetes. 2014 Jan;63(1):188-202. doi: 10.2337/db13-0204. Epub 2013 Oct 2. [ IF= 7.89 ] ]
URL :10.2337/db13-0204
日期:20140217
摘要:Type 1 diabetes is characterized by infiltration of pancreatic islets with immune
cells, leading to insulin deficiency. Although infiltrating immune cells are
traditionally considered to negatively impact beta-cells by promoting their
death, their contribution to proliferation is not fully understood. Here we
report that islets exhibiting insulitis also manifested proliferation of
beta-cells that positively correlated with the extent of lymphocyte infiltration.
Adoptive transfer of diabetogenic CD4(+) and CD8(+) T cells, but not B cells,
selectively promoted beta-cell proliferation in vivo independent from the effects
of blood glucose or circulating insulin or by modulating apoptosis. Complementary
to our in vivo approach, coculture of diabetogenic CD4(+) and CD8(+) T cells with
NOD.RAG1(-/-) islets in an in vitro transwell system led to a dose-dependent
secretion of candidate cytokines/chemokines (interleukin-2 [IL-2], IL-6, IL-10,
MIP-1alpha, and RANTES) that together enhanced beta-cell proliferation. These
data suggest that soluble factors secreted from T cells are potential therapeutic
candidates to enhance beta-cell proliferation in efforts to prevent and/or delay
the onset of type 1 diabetes.

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