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Title: Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intraepithelial lymphocytes in the intestine
Authors: Zhu, Yuanbo
Cui, Guangwei  kyouindb  KAKEN_id
Miyauchi, Eiji
Nakanishi, Yuki  kyouindb  KAKEN_id
Mukohira, Hisa
Shimba, Akihiro
Abe, Shinya
Tani-Ichi, Shizue
Hara, Takahiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Nakase, Hiroshi
Chiba, Tsutomu
Sehara-Fujisawa, Atsuko
Seno, Hiroshi  kyouindb  KAKEN_id
Ohno, Hiroshi
Ikuta, Koichi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 朱, 媛博
崔, 广為
向平, 妃沙
榛葉, 旭恒
阿部, 真也
谷一, 靖江
原, 崇裕
生田, 宏一
Keywords: Bcl-2
Issue Date: May-2020
Publisher: Oxford University Press (OUP)
Journal title: International immunology
Volume: 32
Issue: 5
Start page: 307
End page: 319
Abstract: Interleukin-15 (IL-15) is a cytokine critical for maintenance of intestinal intraepithelial lymphocytes (IELs), especially CD8αα+ IELs (CD8αα IELs). In the intestine, IL-15 is produced by intestinal epithelial cells (IECs), blood vascular endothelial cells (BECs) and hematopoietic cells. However, the precise role of intestinal IL-15 on IELs is still unknown. To address the question, we generated two kinds of IL-15 conditional knockout (IL-15cKO) mice: villin-Cre (Vil-Cre) and Tie2-Cre IL-15cKO mice. IEC-derived IL-15 was specifically deleted in Vil-Cre IL-15cKO mice, whereas IL-15 produced by BECs and hematopoietic cells is deleted in Tie2-Cre IL-15cKO mice. The cell number and frequency of CD8αα IELs and NK IELs were significantly reduced in Vil-Cre IL-15cKO mice. By contrast, CD8αα IELs were unchanged in Tie2-Cre IL-15cKO mice, indicating that IL-15 produced by BECs and hematopoietic cells is dispensable for CD8αα IELs. Expression of an anti-apoptotic factor, Bcl-2, was decreased, whereas Fas expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. Forced expression of Bcl-2 by a Bcl-2 transgene partially restored CD8αα IELs in Vil-Cre IL-15cKO mice, suggesting that some IL-15 signal other than Bcl-2 is required for maintenance of CD8αα IELs. Furthermore, granzyme B production was reduced, whereas PD-1 expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. These results collectively suggested that IEC-derived IL-15 is essential for homeostasis of IELs by promoting their survival and functional maturation.
Rights: This is a pre-copyedited, author-produced version of an article accepted for publication in International immunology following peer review. The version of record Yuanbo Zhu, Guangwei Cui, Eiji Miyauchi, Yuki Nakanishi, Hisa Mukohira, Akihiro Shimba, Shinya Abe, Shizue Tani-ichi, Takahiro Hara, Hiroshi Nakase, Tsutomu Chiba, Atsuko Sehara-Fujisawa, Hiroshi Seno, Hiroshi Ohno, Koichi Ikuta, Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intra-epithelial lymphocytes in the intestine, International Immunology, Volume 32, Issue 5, May 2020, Pages 307–319 is available online at:
The full-text file will be made open to the public on 26 December 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1093/intimm/dxz082
PubMed ID: 31875880
Appears in Collections:Journal Articles

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