Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation

Lim, Ee Lyn; Qian, Yamin; Sugihara, Fuminori et al.

European Journal of Immunology, 2025, 55(10), e70069

アクセス数:10件（2025-12-05 15:50 集計）

固定URL: https://hdl.handle.net/11094/103248

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タイトル
Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation
著者
NRID
1000070822782 1000070822782
著者名
Lim, Ee Lyn
NRID
1000010897317 1000010897317
ORCID
0000-0003-4192-1431 0000-0003-4192-1431
Scopus Author ID
59813354500 59813354500
著者名
Qian, Yamin
NRID
1000050381645 1000050381645
ORCID
0000-0002-6228-4593 0000-0002-6228-4593
researchmap permalink
sugiharaf sugiharaf
Scopus Author ID
12809512100 12809512100
著者名
Sugihara, Fuminori
NRID
1000000724105 1000000724105
ORCID
0000-0003-1660-9892 0000-0003-1660-9892
researchmap permalink
TanakaAtsushi TanakaAtsushi
Scopus Author ID
56647343500 56647343500
著者名
Tanaka, Atsushi
NRID
1000030280770 1000030280770
ORCID
0000-0001-8265-6094 0000-0001-8265-6094
researchmap permalink
read0192931 read0192931
Scopus Author ID
7201357958 7201357958
著者名
Sakaguchi, Shimon
キーワード等
autoimmunity
immune regulation
PI-3-kinase-δ
regulatory T cells
内容
Lim E.L., Qian Y., Sugihara F., et al. Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation. European Journal of Immunology 55, e70069 (2025); https://doi.org/10.1002/eji.70069.
抄録
Peripherally derived regulatory T cells (pTregs) have a prominent role in maintaining intestinal immune homeostasis. In cases of phosphoinositide-3-kinase δ (PI3Kδ) inactivation, such as in patients receiving PI3Kδ inhibitor idelalisib as a cancer treatment, breakdown of intestinal immune tolerance occurs frequently in the form of diarrhea and colon inflammation. In a mouse model of systemic PI3Kδ inactivation, both enhancement of antitumor immunity and colitis have been described as a result of Treg impairment. However, in view of the critical role for Tregs in the prevention of systemic autoimmunity, the basis for such tissue-restricted breach of immune tolerance upon loss of PI3Kδ function is not yet understood. We report here that mice lacking PI3Kδ activity do not suffer a general defect in Treg immunosuppression, but specifically fail to develop Helios− pTregs in the colon. We demonstrate reduced extrathymic Treg induction, in vitro and in vivo, from naïve CD4⁺ T cells with inactive PI3Kδ, along with dysregulation of a tissue-resident phenotype. These results suggest a nonredundant role for PI3Kδ-dependent pTreg differentiation in maintaining tolerance to commensal microbial antigens in the gut.
出版者
John Wiley and Sons Inc
収録物名
European Journal of Immunology
巻(号)
55(10)
ページ
e70069
刊行年月
2025-10-06
言語
英語
ハンドルURL
https://hdl.handle.net/11094/103248
PISSN
00142980
eISSN
15214141
関連情報 (isIdenticalTo)
DOI (出版社版)
https://doi.org/10.1002/eji.70069
アクセス権
open access
権利情報
This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ
Version of Record
カテゴリ
学術雑誌論文 Journal Article