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- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
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581
Dendritic cell functions and characteristic gene expression
profiles in hepatitis B virus-infected patients
Atsushi Yonejima, Eishiro Mizukoshi, Yuki Inada, Akihiko Kida,
Kiichiro Kaji, Kazutoshi Yamada, Toshikatsu Tamai, Hidetoshi
Nakagawa, Takeshi Terashima, Noriho Iida, Masaaki Kitahara,
Masao Honda, Shuichi Kaneko; gastroenterology, Kanazawa University,
Kanazawa City, Japan
Background and Aims Hepatitis B virus (HBV) has been
reported to suppress immune function of dendritic cells (DCs).
Although the inhibitory mechanism of this suppression has
started to become clear, the complete picture remains unclear.
This study investigated DC functions and characteristic gene
expression profiles in HBV-infected patients. Material and
Methods Peripheral blood mononuclear cells (PBMCs) were
collected from 58 HBV-infected patients and 19 healthy individuals.
PBMCs were labeled with antibodies against HLA-DR,
Lin-1, CD123 and CD11c, and fluorescence-activated cell
sorting (FACS) was used to sort DCs into plasmacytoid DCs
(pDCs) and myeloid DCs (mDCs) and to measure expression
levels of cell surface markers. To examine DC functions
in different pathological conditions, phagocytic activity and
migration activity were measured using a phagocytosis assay
kit and by cell migration assay, respectively, and compared
between HBV-infected patients and healthy individuals. Further,
mRNAs were extracted from FACS-sorted pDCs and mDCs
from 7 healthy individuals, 7 HBV carriers with normal liver
function, 6 untreated chronic hepatitis patients and 12 chronic
hepatitis patients on treatment with a nucleic acid analogue,
and subjected to gene expression analysis. Results In HBV-infected
patients, the number of mDCs was lower and the expression
levels of CD80, CD83, CD40 and CCR7 were higher
compared to normal individuals. Comparison of DC functions
between different pathological conditions revealed that both
phagocytic activity and migration activity tended to be higher
in healthy individuals than in HBV-infected patients. Gene
expression analysis identified 1,000 genes downregulated
with HBV infection, 33 of which were immune-related genes.
Among these 33 genes, 6 genes, of which expression levels
were particularly decreased in untreated patients with chronic
hepatitis, but slightly reverted after treatment, were further identified.
IL-6ST (gp160) gene was one of these 6 genes, and its
expression level positively correlated with expression levels of
CD80 CD83, CD86, CD40, and CCR7 in mDCs and pDCs,
and also, associated with some part of DC function. Conclusions
We found that HBV infection causes marked changes in
the number of DCs, surface marker expression, function, and
gene expression levels. We also identified gene expression
profiles unique to individual pathological conditions in patients
with chronic hepatitis B. Taken together, this study identified
a number of genes that influence DC function in patients with
chronic hepatitis B, and revealed in particular that the expression
level of the IL-6SR (gp130) gene is associated with DC
function.
Disclosures:
Shuichi Kaneko - Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co.,
Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc,
Ajinomoto Co., Inc, Bristol Myers Squibb., Inc, Pfizer., Co., Inc, Astellas., Inc,
Takeda., Co., Inc, Otsuka„ÄÄPharmaceutical, Co., Inc, Eizai Co., Inc, Bayer
Japan, Eli lilly Japan
The following people have nothing to disclose: Atsushi Yonejima, Eishiro
Mizukoshi, Yuki Inada, Akihiko Kida, Kiichiro Kaji, Kazutoshi Yamada, Toshikatsu
Tamai, Hidetoshi Nakagawa, Takeshi Terashima, Noriho Iida, Masaaki
Kitahara, Masao Honda
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发表于 2016-10-11 20:25