| RRC ID |
81957
|
| Author |
Matsumoto R, Ogata K, Takahashi D, Kinashi Y, Yamada T, Morita R, Tanaka K, Hattori K, Endo M, Fujimura Y, Sasaki N, Ohno H, Ishihama Y, Kimura S, Hase K.
|
| Title |
AP-1B regulates interactions of epithelial cells and intraepithelial lymphocytes in the intestine.
|
| Journal |
Cell Mol Life Sci
|
| 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.
|
| Volume |
81(1)
|
| Pages |
425
|
| Published |
2024-10-5
|
| DOI |
10.1007/s00018-024-05455-1
|
| PII |
10.1007/s00018-024-05455-1
|
| PMID |
39369131
|
| PMC |
PMC11455912
|
| MeSH |
Adaptor Protein Complex 1* / genetics
Adaptor Protein Complex 1* / metabolism
Animals
Antigens, CD* / genetics
Antigens, CD* / metabolism
Cell Adhesion Molecules, Neuronal / genetics
Cell Adhesion Molecules, Neuronal / metabolism
Cell Communication
Epithelial Cells* / immunology
Epithelial Cells* / metabolism
Intestinal Mucosa* / cytology
Intestinal Mucosa* / immunology
Intestinal Mucosa* / metabolism
Intestines / cytology
Intestines / immunology
Intraepithelial Lymphocytes* / immunology
Intraepithelial Lymphocytes* / metabolism
Mice
Mice, Inbred C57BL
|
| Resource |
| DNA material |
pENTR4-H1 (RDB04395)
CSII-EF-mRFP1 (RDB06387)
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
