789 - Enteric Pathogens Induce M Cell Transcytosis in a Human Enteroid Model of the Follicle Associated Epithelium

2018 ◽  
Vol 154 (6) ◽  
pp. S-164
Author(s):  
Michele Doucet ◽  
Janet Staab ◽  
Sridevi Ranganathan ◽  
Olga Kovbasnjuk ◽  
James Kaper ◽  
...  
Keyword(s):  
Enteric Pathogens ◽  
M Cell ◽  
Follicle Associated Epithelium

scholarly journals Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling

2018 ◽  
Vol 215 (2) ◽  
pp. 501-519 ◽  
Author(s):  
Takashi Kanaya ◽  
Sayuri Sakakibara ◽  
Toshi Jinnohara ◽  
Masami Hachisuka ◽  
Naoko Tachibana ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Tumor Necrosis Factor Receptor ◽  
M Cells ◽  
M Cell ◽  
Antigen Uptake ◽  
Conditional Deletion ◽  
Follicle Associated Epithelium ◽  
Necrosis Factor

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer’s patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell–associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor–associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.

scholarly journals Identifying human and murine M cells in vitro

2019 ◽  
Vol 244 (7) ◽  
pp. 554-564 ◽  
Author(s):  
Ana Klisuric ◽  
Benjamin Thierry ◽  
Ludivine Delon ◽  
Clive A Prestidge ◽  
Rachel J Gibson
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
In Vitro Models ◽  
Oral Drug ◽  
M Cells ◽  
Cell Marker ◽  
M Cell ◽  
Follicle Associated Epithelium

M cells are an epithelial cell population found in the follicle-associated epithelium overlying gut-associated lymphoid tissues. They are specialized in the transcytosis of luminal antigens. Their transcytotic capacity and location in an immunocompetent environment has prompted the study of these cells as possible targets for oral drug delivery systems. Currently, the models most commonly used to study M cells are restricted to in vivo experiments conducted in mice, and in vitro studies conducted in models comprised either of primary epithelial cells or established cell lines of murine or human origin. In vitro models of the follicle-associated epithelium can be constructed in several ways. Small intestinal Lgr5+ stem cells can be cultured into a 3D organoid structure where M cells are induced with RANKL administration. Additionally, in vitro models containing an “M cell-like” population can be obtained through co-culturing intestinal epithelial cells with cells of lymphocytic origin to induce the M cell phenotype. The evaluation of the efficiency of the variations of these models and their relevance to the in vivo human system is hampered by the lack of a universal M cell marker. This issue has also hindered the advancement of M cell-specific targeting approaches aimed at improving the bioavailability of orally administered compounds. This critical review discusses the different approaches utilized in the literature to identify M cells, their efficiency, reliability and relevance, in the context of commonly used models of the follicle-associated epithelium. The outcome of this review is a clearly defined and universally recognized criteria for the assessment of the relevance of models of the follicle-associated models currently used. Impact statement The study of M cells, a specialized epithelial cell type found in the follicle-associated epithelium, is hampered by the lack of a universal M cell marker. As such, many studies lack reliable and universally recognized methods to identify M cells in their proposed models. As a result of this it is difficult to ascertain whether the effects observed are due to the presence of M cells or an unaccounted variable. The outcome of this review is the thorough evaluation of the many M cell markers that have been used in the literature thus far and a proposed criterion for the identification of M cells for future publications. This will hopefully lead to an improvement in the quality of future publications in this field.

153 – Coronin 1 is Necessary for M Cell Transcytosis in a Human Enteroid Model of the Follicle Associated Epithelium

2019 ◽  
Vol 156 (6) ◽  
pp. S-36
Author(s):  
Michele Doucet ◽  
Rachel Latanich ◽  
Janet Staab ◽  
Sridevi Ranganathan ◽  
Eileen Barry ◽  
...  
Keyword(s):  
M Cell ◽  
Follicle Associated Epithelium

scholarly journals TNF-α augments RANKL-dependent intestinal M cell differentiation in enteroid cultures

2016 ◽  
Vol 311 (3) ◽  
pp. C498-C507 ◽  
Author(s):  
Megan B. Wood ◽  
Daniel Rios ◽  
Ifor R. Williams
Keyword(s):  
Cell Differentiation ◽  
Protein Kinase ◽  
Three Dimensional ◽  
Mitogen Activated Protein Kinase ◽  
M Cells ◽  
Epithelial Stem Cells ◽  
M Cell ◽  
Gene Encoding ◽  
Tnf Α ◽  
Follicle Associated Epithelium

Microfold (M) cells are phagocytic intestinal epithelial cells in the follicle-associated epithelium of Peyer's patches that transport particulate antigens from the gut lumen into the subepithelial dome. Differentiation of M cells from epithelial stem cells in intestinal crypts requires the cytokine receptor activator of NF-κB ligand (RANKL) and the transcription factor Spi-B. We used three-dimensional enteroid cultures established with small intestinal crypts from mice as a model system to investigate signaling pathways involved in M cell differentiation and the influence of other cytokines on RANKL-induced M cell differentiation. Addition of RANKL to enteroids induced expression of multiple M cell-associated genes, including Spib, Ccl9 [chemokine (C-C motif) ligand 9], Tnfaip2 (TNF-α-induced protein 2), Anxa5 (annexin A5), and Marcksl1 (myristoylated alanine-rich protein kinase C substrate) in 1 day. The mature M cell marker glycoprotein 2 ( Gp2) was strongly induced by 3 days and expressed by 11% of cells in enteroids. The noncanonical NF-κB pathway was required for RANKL-induced M cell differentiation in enteroids, as addition of RANKL to enteroids from mice with a null mutation in the mitogen-activated protein kinase kinase kinase 14 ( Map3k14) gene encoding NF-κB-inducing kinase failed to induce M cell-associated genes. While the cytokine TNF-α alone had little, if any, effect on expression of M cell-associated genes, addition of TNF-α to RANKL consistently resulted in three- to sixfold higher levels of multiple M cell-associated genes than RANKL alone. One contributing mechanism is the rapid induction by TNF-α of Relb and Nfkb2 (NF-κB subunit 2), genes encoding the two subunits of the noncanonical NF-κB heterodimer. We conclude that endogenous activators of canonical NF-κB signaling present in the gut-associated lymphoid tissue microenvironment, including TNF-α, can play a supportive role in the RANKL-dependent differentiation of M cells in the follicle-associated epithelium.

scholarly journals IL-22BP dictates characteristics of Peyer’s patch follicle-associated epithelium for antigen uptake

2017 ◽  
Vol 214 (6) ◽  
pp. 1607-1618 ◽  
Author(s):  
Toshi Jinnohara ◽  
Takashi Kanaya ◽  
Koji Hase ◽  
Sayuri Sakakibara ◽  
Tamotsu Kato ◽  
...  
Keyword(s):  
Cell Function ◽  
Lymphoid Tissues ◽  
Antimicrobial Proteins ◽  
M Cell ◽  
Antigen Uptake ◽  
Interleukin 22 ◽  
Follicle Associated Epithelium ◽  
Enhanced Expression ◽  
Bacterial Uptake ◽  
And Function

Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α− dendritic cells in the subepithelial dome region of Peyer’s patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP–deficient (Il22ra2−/−) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2−/− mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.

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