scholarly journals M cell-dependent antigen uptake on follicle-associated epithelium for mucosal immune surveillance

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Yutaka Nakamura ◽  
Shunsuke Kimura ◽  
Koji Hase
Keyword(s):  
Immune Surveillance ◽  
M Cell ◽  
Antigen Uptake ◽  
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 Characterization of M Cells in Tear Duct-Associated Lymphoid Tissue of Mice: A Potential Role in Immunosurveillance on the Ocular Surface

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuki Oya ◽  
Shunsuke Kimura ◽  
Yutaka Nakamura ◽  
Narumi Ishihara ◽  
Shunsuke Takano ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymphoid Tissue ◽  
Immune Surveillance ◽  
Small Population ◽  
M Cells ◽  
Eye Drops ◽  
M Cell ◽  
Antigen Uptake ◽  
Mucosal Tissues ◽  
Eye Region

The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8+ M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization via eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.

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.

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 Uptake of Ferritin by Follicle-associated Epithelium in the Colon of Calves

1992 ◽  
Vol 29 (2) ◽  
pp. 120-128 ◽  
Author(s):  
M. Paar ◽  
E. M. Liebler ◽  
J. F. Pohlenz
Keyword(s):  
Small Intestine ◽  
Large Intestine ◽  
M Cells ◽  
Multivesicular Bodies ◽  
Ascending Colon ◽  
Intercellular Spaces ◽  
Antigen Uptake ◽  
Follicle Associated Epithelium ◽  
Apical Vesicles ◽  
Lymphoid Nodules

Uptake of macromolecules (e.g., ferritin) by M cells in follicle-associated epithelium in small and large intestine was investigated in three healthy, conventionally raised, 2- to 3-week-old, female Holstein Frisian calves. A 2.5% solution of ferritin was injected into the ligated loops in mid-jejunum, in terminal ileum, in the ascending colon adjacent to the ileocecal junction, and in the proximal loop of the ascending colon containing gut-associated lymphoid tissue. After exposure times that ranged from 82 to 165 minutes, ferritin was detected in M cells of domes in the small intestine, as well as in cells in follicle-associated epithelium of proprial lymphoid nodules and lymphoglandular complexes of colon that morphologically resembled M cells of small intestine. Ferritin was found in apical invaginations, apical vesicles, multivesicular bodies, basal vesicles, and adjacent intercellular spaces. In addition to ferritin, apical vesicles, multivesicular bodies, and intercellular spaces contained 50-nm membrane-bound particles. More ferritin was endocytosed by M cells of the small intestine than by M cells of the large intestine. In the large intestine, higher amounts of ferritin were found in M cells of follicle-associated epithelium overlying proprial lymphoid nodules than in M cells of follicle-associated epithelium in the depth of lymphoglandular complexes. Based on these results, we concluded that M cells of follicle-associated epithelium in the colon of calves provide a route for antigen uptake into the intestinal lymphoid system.

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 M CELLS ARE THE IMPORTANT POST IN THE INITIATION OF IMMUNE RESPONSE IN INTESTINE

2018 ◽  
Vol 8 (3) ◽  
pp. 263-272
Author(s):  
A. S. Bykov ◽  
A. V. Karaulov ◽  
D. A. Tsomartova ◽  
N. L. Kartashkina ◽  
V. L. Goriachkina ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Targeted Delivery ◽  
Oral Vaccine ◽  
Critical Event ◽  
M Cells ◽  
M Cell ◽  
Antigen Uptake ◽  
And Function

Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically "target" antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.

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