| Item type |
学内発行雑誌 / Departmental Bulletin Paper(1) |
| 公開日 |
2016-11-28 |
| タイトル |
|
|
タイトル |
Features of and Mechanisms Underlying Insulitis In aly/aly Male Mice as an Animal Model of Autoimmune Pancreatitis: Activation of CD11c+, CD4+, and Th2 Cells and Predominant Destruction of β-cells |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ |
departmental bulletin paper |
| 著者 |
SATO, Yoshiki
YOSHIDA, Hitoshi
TANAKA, Shigeki
NOMOTO, Tomohiro
HONMA, Tadashi
IWATA, Tomoyuki
YAMAZAKI, Takahisa
YUKAWA, Akihiro
KITAMURA, Katsuya
IMAMURA, Tsunao
IKEGAMI, Akitoshi
IMAWARI, Michio
|
| 書誌情報 |
The Showa University journal of medical sciences
巻 24,
号 2,
p. 139-153,
発行日 2012-06
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Diabetes mellitus (DM) is observed in patients with autoimmune pancreatitis (AIP). The development of DM in AIP is believed to be due to blood flow obstruction of the endocrine gland that accompanies pancreatitis, as well as injury to the islets caused by inflammation. The latter is called insulitis and the detailed mechanisms underlying its development are not yet clear. The aim of the present study was to elucidate the mechanisms involved in the development of insulitis in AIP using aly mice as an animal model of AIP: results in aly/aly male mice, as the AIP group, were compared with those inaly/+ male mice as a control group. Mice in both groups were killed between 16 and 48 weeks of age, and pancreatitis and insulitis were evaluated histologically. Inflammatory and endocrine cells were evaluated by immunofluorescence staining with anti-CD4, anti-CD8, anti-CD11b, and anti-CD11c antibodies, as well as immunohistochemical analyses using insulin and glucagon antibodies. Plasma levels and the pancreatic content of interferon (IFN)-γ (as a Th1-secreted cytokine) and interleukin (IL)-4 (as a Th2-secreted cytokine) were determined. Pancreatitis was seen in aly/aly mice from 16 weeks of age and it developed gradually thereafter. Insulitis also developed gradually and was seen in mice after 24 weeks of age in association with a decrease in the number of islets. CD11c+ cells and CD4+ T cells were seen to infiltrate into the islets. Although the number of β-cells decreased with time, the number of α-cells was maintained until mice were 48 weeks of age. IFN-γ content peaked in mice at 16 weeks of age and declined rapidly from 20 weeks. There were two peaks in IL-4 content, one at 16 weeks and the other at 32 weeks, suggesting an association between IL-4 content and advanced insulitis after 32 weeks. In conclusion, the results suggest that insulitis in AIP is induced predominantly by the infiltration of CD11c+ cells and CD4+ T cells into the islets, and progression is facilitated by the imbalance of the activation of Th2 rather than Th1. Furthermore, insulitis in AIP predominantly involves β-cells rather than α-cells. |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
関連識別子 |
10.15369/sujms.24.139 |
| 出版者 |
|
|
出版者 |
Showa Medical Association and Showa University |
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0915-6380 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
S24_139.pdf (1.2 MB)
