AP-1B regulates interactions of epithelial cells and intraepithelial lymphocytes in the intestine

Intraepithelial lymphocytes (IELs) reside in the epithelial layer and protect against foreign pathogens, maintaining the epithelial barrier function in the intestine. Interactions between IEL and epithelial cells are required for IELs to function effectively; however, the underlying molecular machin...

Full description

Saved in:
Bibliographic Details
Published inCellular and molecular life sciences : CMLS Vol. 81; no. 1; p. 425
Main Authors Matsumoto, Ryohtaroh, Ogata, Kosuke, Takahashi, Daisuke, Kinashi, Yusuke, Yamada, Takahiro, Morita, Ryo, Tanaka, Keisuke, Hattori, Kouya, Endo, Mayumi, Fujimura, Yumiko, Sasaki, Nobuo, Ohno, Hiroshi, Ishihama, Yasushi, Kimura, Shunsuke, Hase, Koji
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.12.2024
Springer Nature B.V
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Intraepithelial lymphocytes (IELs) reside in the epithelial layer and protect against foreign pathogens, maintaining the epithelial barrier function in the intestine. Interactions between IEL and epithelial cells are required for IELs to function effectively; however, the underlying molecular machinery remains to be elucidated. In this study, we found that intestinal epithelium-specific deficiency of the clathrin adaptor protein (AP)-1B, which regulates basolateral protein sorting, led to a massive reduction in IELs. Quantitative proteomics demonstrated that dozens of proteins, including known IEL-interacting proteins (E-cadherin, butyrophilin-like 2, and plexin B2), were decreased in the basolateral membrane of AP-1B-deficient epithelial cells. Among these proteins, CD166 interacted with CD6 on the surface of induced IEL. CD166 knockdown, using shRNA in intestinal organoid cultures, significantly inhibited IEL recruitment to the epithelial layer. These findings highlight the essential role of AP-1B-mediated basolateral sorting in IEL maintenance and survival within the epithelial layer. This study reveals a novel function of AP-1B in the intestinal immune system.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1420-682X
1420-9071
1420-9071
DOI:10.1007/s00018-024-05455-1