Inducible Colonic M Cells Are Dependent on TNFR2 but Not Ltβr, Identifying Distinct Signalling Requirements for Constitutive Versus Inducible M Cells

Parnell, Erinn; Walch, Erin; Lo, David

doi:10.1093/ecco-jcc/jjw212

Cited by 9 publications

(13 citation statements)

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“…At present, the mechanisms by which inflammatory cytokines and infectious models (such as Salmonella and C. rodentium ) induce M-cells are not well-understood 51–53 . Overexpression of p52-RelB failed to induce M-cells and similarly, constitutive epithelial NIK signaling was not sufficient to increase M-cells in PP or colon LF.…”

Section: Discussionmentioning

confidence: 99%

Intestinal non-canonical NFκB signaling shapes the local and systemic immune response

Ramakrishnan

Zhang

et al. 2019

Nat Commun

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Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.

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Section: Discussionmentioning

confidence: 99%

Intestinal non-canonical NFκB signaling shapes the local and systemic immune response

Ramakrishnan

Zhang

et al. 2019

Nat Commun

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“…Yet another subset of stromal cells in a discrete layer below the FAE expresses the cytokine RANKL (92, 93). This cytokine has been shown to correlate with M cell induction, and in organoid cultures, addition of exogenous RANKL was sufficient to induce functional M cell development (31, 33, 94–96).…”

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

confidence: 98%

“…Moreover, while organoid cultures confirm the requirement for RANKL in M cell induction, the location of RANKL+ stromal cells in Peyer's patches is curious. Instead of being located immediately adjacent to the crypts, they appear to be predominantly in the subepithelial dome region (96) (Figure 5). Thus, while RANKL may have a role in crypt cell induction and lineage commitment (Step 1 in the two step model), the anatomy of RANKL expression suggests that RANKL, instead of being simply an early inducer of crypt stem cells, may also provide reinforcement of an early M cell lineage commitment (induced how?…”

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

confidence: 99%

“…Peyer's patch showing FAE M cells (red) with underlying array of RANKL+ stromal cells (yellow). Note that RANKL staining is strongest under the main concentration of M cells rather than near adjacent crypt stem cells [reprinted from Parnell et al (96) with permission].…”

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

confidence: 99%

“…Therefore, to study whether chronic inflammation may indeed induce new M cell development, two models of intestinal inflammation were studied. One was an infection by Citrobacter that produces a limited infectious colitis, and the other was the Dextran Sodium Sulfate (DSS) model, in which DSS in the drinking water results in epithelial barrier disruption and chronic inflammation (96, 112). In both models, colonic lamina propria inflammation was induced, and M cell numbers were significantly increased.…”

Section: Life History Of Inducible M Cells In Chronic Inflammationmentioning

confidence: 99%

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M Cells: Intelligent Engineering of Mucosal Immune Surveillance

Dillon

2019

Front. Immunol.

Self Cite

134

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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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Intestinal Peyer’s Patches: Structure, Function, and In Vitro Modeling

Park

Cho

Kang

2023

Tissue Eng Regen Med

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Backgound: Considering the important role of the Peyer’s patches (PPs) in gut immune balance, understanding of the detailed mechanisms that control and regulate the antigens in PPs can facilitate the development of immune therapeutic strategies against the gut inflammatory diseases. Methods: In this review, we summarize the unique structure and function of intestinal PPs and current technologies to establish in vitro intestinal PP system focusing on M cell within the follicle-associated epithelium and IgA + B cell models for studying mucosal immune networks. Furthermore, multidisciplinary approaches to establish more physiologically relevant PP model were proposed. Results: PPs are surrounded by follicle-associated epithelium containing microfold (M) cells, which serve as special gateways for luminal antigen transport across the gut epithelium. The transported antigens are processed by immune cells within PPs and then, antigen-specific mucosal immune response or mucosal tolerance is initiated, depending on the response of underlying mucosal immune cells. So far, there is no high fidelity (patho)physiological model of PPs; however, there have been several efforts to recapitulate the key steps of mucosal immunity in PPs such as antigen transport through M cells and mucosal IgA responses. Conclusion: Current in vitro PP models are not sufficient to recapitulate how mucosal immune system works in PPs. Advanced three-dimensional cell culture technologies would enable to recapitulate the function of PPs, and bridge the gap between animal models and human.

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Inducible Colonic M Cells Are Dependent on TNFR2 but Not Ltβr, Identifying Distinct Signalling Requirements for Constitutive Versus Inducible M Cells

Cited by 9 publications

References 50 publications

Intestinal non-canonical NFκB signaling shapes the local and systemic immune response

Intestinal non-canonical NFκB signaling shapes the local and systemic immune response

M Cells: Intelligent Engineering of Mucosal Immune Surveillance

Intestinal Peyer’s Patches: Structure, Function, and In Vitro Modeling

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