c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

Sehgal, Anuj; Kobayashi, Atsushi; Donaldson, David S.; Mabbott, Neil A.

doi:10.1016/j.imbio.2016.09.008

Cited by 7 publications

(5 citation statements)

References 62 publications

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“…Because NIK acts as a specific component of the non-canonical NF-κB pathway [ 48 ], this result suggested that the RANKL-induced non-canonical NF-κB pathway is essential for M cell differentiation. Recent studies reported that M cell differentiation was dependent on non-canonical RelB pathway, but not canonical c-Rel [ 46 , 47 , 49 ]. However, the canonical NF-κB pathway supports M cell differentiation by enhancing the expression of Relb and Nfkb2 in enteroids stimulated with TNF-α [ 47 ].…”

Section: Differentiation Of M Cellsmentioning

confidence: 99%

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

2018

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The follicle-associated epithelium (FAE) covering mucosa-associated lymphoid tissue is distinct from the villous epithelium in cellular composition and functions. Interleukin-22 binding protein (IL-22BP), provided by dendritic cells at the sub-epithelial dome region, inhibits the IL-22-mediated secretion of antimicrobial peptides by the FAE. The Notch signal from stromal cells underneath the FAE diminishes goblet cell differentiation. These events dampen the mucosal barrier functions to allow luminal microorganisms to readily gain access to the luminal surface of the FAE. Furthermore, receptor activator of nucleic factor-kappa B ligand (RANKL) from a certain stromal cell type induces differentiation into microfold (M) cells that specialize in antigen uptake in the mucosa. Microfold (M) cells play a key role in mucosal immune surveillance by actively transporting external antigens from the gut lumen to the lymphoid follicle. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. For example, GPI-anchored molecules (e.g., glycoprotein 2 (GP2) and cellular prion protein (PrPC)) and β1-integrin facilitate the transport of specific types of xenobiotics. The antigen transport by M cells initiates antigen-specific mucosal immune responses represented by the induction of secretory immunoglobulin A (S-IgA). Meanwhile, several invasive pathogens exploit M cells as a portal to establish a systemic infection. Recent findings have uncovered the molecular machinery of differentiation and functions of M cells.

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Section: Differentiation Of M Cellsmentioning

confidence: 99%

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

2018

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“…Amongst these, the RANKL-mediated activation of the non-canonical NF-κB pathway TF family members NF-κB2 and RelB, and canonical NF-κB pathway TF family members NF-κB1 and RelA, is essential for M cell differentiation ( 18 , 40 ). Activation of c-Rel, in contrast, is dispensable for M cell-differentiation in Peyer’s patches ( 41 ). As anticipated, many of the genes in Cluster 003 were significantly enriched with NF-κB family TF binding site motifs, including RelA and RelB ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

Aging-Related Impairments to M Cells in Peyer’s Patches Coincide With Disturbances to Paneth Cells

2021

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The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer’s patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer’s patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer’s patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.

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“…The effect of organized lymphoid tissues, LTi, and local RANKL production on the adjacent crypt stem cells produces a variety of cell phenotypes in the Follicle Associated Epithelium (FAE) (38); one or more of the TNF related cytokines produced by LTi (as well as FRC and other cells) may account for FAE being uniformly positive for NF-κB activation and relB expression (99–101). Yet this global activation of FAE does not explain the sequence of events resulting in crypt cell commitment of a specific subset of enterocytes to M cell production.…”

Section: Organized Lymphoid Tissues and The Life History Of “Constitumentioning

confidence: 99%

M Cells: Intelligent Engineering of Mucosal Immune Surveillance

Dillon

2019

Front. Immunol.

136

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M cells are specialized intestinal epithelial cells that provide the main machinery for sampling luminal microbes for mucosal immune surveillance. M cells are usually found in the epithelium overlying organized mucosal lymphoid tissues, but studies have identified multiple distinct lineages of M cells that are produced under different conditions, including intestinal inflammation. Among these lineages there is a common morphology that helps explain the efficiency of M cells in capturing luminal bacteria and viruses; in addition, M cells recruit novel cellular mechanisms to transport the particles across the mucosal barrier into the lamina propria, a process known as transcytosis. These specializations used by M cells point to a novel engineering of cellular machinery to selectively capture and transport microbial particles of interest. Because of the ability of M cells to effectively violate the mucosal barrier, the circumstances of M cell induction have important consequences. Normal immune surveillance insures that transcytosed bacteria are captured by underlying myeloid/dendritic cells; in contrast, inflammation can induce development of new M cells not accompanied by organized lymphoid tissues, resulting in bacterial transcytosis with the potential to amplify inflammatory disease. In this review, we will discuss our own perspectives on the life history of M cells and also raise a few questions regarding unique aspects of their biology among epithelia.

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c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

Cited by 7 publications

References 62 publications

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

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

Aging-Related Impairments to M Cells in Peyer’s Patches Coincide With Disturbances to Paneth Cells

M Cells: Intelligent Engineering of Mucosal Immune Surveillance

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