AP-1B Regulates Interactions of Epithelial Cells and Intraepithelial Lymphocytes in the Intestine

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2024 Oct 5

PMID 39369131

Authors

Ryohtaroh Matsumoto

Kosuke Ogata

Daisuke Takahashi

Yusuke Kinashi

Takahiro Yamada

Ryo Morita

Keisuke Tanaka

Kouya Hattori

Mayumi Endo

Yumiko Fujimura

Nobuo Sasaki

Hiroshi Ohno

Yasushi Ishihama

Shunsuke Kimura

Koji Hase

Affiliations

Soon will be listed here.

Abstract

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.

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