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 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.
Authors
- Yasushi Ishihama (ORCID: https://orcid.org/0000-0001-7714-203X)
- Ryohtaroh Matsumoto
- Keisuke Tanaka (ORCID: https://orcid.org/0000-0003-0658-7781)
- Kouya Hattori (ORCID: https://orcid.org/0000-0002-1932-123X)
- Mayumi Endo (ORCID: https://orcid.org/0000-0002-7191-0314)
- Koji Hase (ORCID: https://orcid.org/0000-0001-9550-2334)
- Nobuo Sasaki (ORCID: https://orcid.org/0000-0002-8798-7244)
- Ryo Morita (ORCID: https://orcid.org/0000-0002-4746-3163)
- Kosuke Ogata (ORCID: https://orcid.org/0000-0002-0634-3990)
- Hiroshi Ohno (ORCID: https://orcid.org/0000-0001-8776-9661)
- Shunsuke Kimura (ORCID: https://orcid.org/0000-0001-9408-2884)
- Yusuke Kinashi
- Daisuke Takahashi (ORCID: https://orcid.org/0000-0001-8624-1160)
- Takahiro Yamada (ORCID: https://orcid.org/0000-0003-2613-5600)
- Yumiko Fujimura
Institutions
- Gunma University (JP)
- Keio University (JP)
- Kyoto University (JP)
- National Institute of Biomedical Innovation, Health and Nutrition (JP)
- Japan Science and Technology Agency (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Fukushima University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Cellular and Molecular Life Sciences
- Published
- 2024-10-05
- DOI
- https://doi.org/10.1007/s00018-024-05455-1
- Citations
- 1
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 0.28
Funders
- Asahi Glass Foundation
- Fuji Foundation for Protein Research
- Japan Agency for Medical Research and Development
- Keio University
- Secom Science and Technology Foundation
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology
- Moonshot Research and Development Program