Journal
CYTOKINE
Volume 47, Issue 1, Pages 69-76Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2009.05.001
Keywords
Lymphotoxin; Tumor necrosis factor; Mucosal immunity; Epithelium
Funding
- NIH [AI63426, AI73689]
- Bill and Melinda Gates Foundation/Foundation for the National Institutes of Health
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M cells assist mucosal immune surveillance by transcytosis of particles to underlying lymphoid tissue, but the mechanisms of M cell differentiation are poorly understood. To develop a better defined cell culture model of M cell differentiation, we treated human (Caco-2BBe) and rat (IEC-6) intestinal epithelial cell lines with lymphotoxin beta receptor (LT beta R) and TNF receptor (TNFR) agonists. Treated cells were studied for regulation of genes associated with M cell and follicle-associated epithelium (FAE). We found that LT beta R and TNFR agonists induce transcription of FAE-specific genes (Ccl20 and Lamb3) in Caco2-BBe cells and IEC-6 cells as well as rodent M cell specific genes such as Sgne-1/Scg5, Cldn4, and Gp2. The cytokines have distinct but complementary effects; TNFR agonists mainly induced FAE-specific genes, while the LT beta R agonist induced M cell specific genes. The combination of cytokines showed additive induction of the FAE-associated Ccl20, Lamb3 and a surprising induction of CD137/Tnfrsf9. On the other hand TNF agonists appeared to suppress expression of some LT beta R-induced genes. Functionally, cytokine treatment led to the reorganization of microvilli and Claudin-4 redistribution. These studies suggest complex interactions between these cytokines in the context of either inflammation or tissue differentiation. (C) 2009 Elsevier Ltd. All rights reserved.
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