Peptidoglycan recognition protein expression in mouse Peyer’s Patch follicle associated epithelium suggests functional specialization

Lo, David; Tynan, Wendy; Dickerson, Janet; Mendy, Jason; Chang, Hwai-Wen; Scharf, Melinda; Byrne, Daragh; Brayden, David J.; Higgins, Lisa; Evans, Claire F.; O’Mahony, Donagh

doi:10.1016/s0008-8749(03)00155-2

Cited by 68 publications

(48 citation statements)

References 40 publications

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“…In contrast, the apical and basal distribution of TLR2 and TLR9 on the FAE may reflect the presence of microorganisms and their components on both sides of the epithelial barrier as a result of constitutive transepithelial transport by M cells. For the recognition of PGN in particular, other receptors such as peptidoglycan recognition protein (PGRP)-L and PGRP-S, which are exclusively expressed on the FAE cells, may also be involved (51).…”

Section: Discussionmentioning

confidence: 99%

TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Chabot

Wagner

Farrant

et al. 2006

The Journal of Immunology

139

116

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Initiation of adaptive mucosal immunity occurs in organized mucosal lymphoid tissues such as Peyer’s patches of the small intestine. Mucosal lymphoid follicles are covered by a specialized follicle-associated epithelium (FAE) that contains M cells, which mediate uptake and transepithelial transport of luminal Ags. FAE cells also produce chemokines that attract Ag-presenting dendritic cells (DCs). TLRs link innate and adaptive immunity, but their possible role in regulating FAE functions is unknown. We show that TLR2 is expressed in both FAE and villus epithelium, but TLR2 activation by peptidoglycan or Pam3Cys injected into the intestinal lumen of mice resulted in receptor redistribution in the FAE only. TLR2 activation enhanced transepithelial transport of microparticles by M cells in a dose-dependent manner. Furthermore, TLR2 activation induced the matrix metalloproteinase-dependent migration of subepithelial DCs into the FAE, but not into villus epithelium of wild-type and TLR4-deficient mice. These responses were not observed in TLR2-deficient mice. Thus, the FAE of Peyer’s patches responds to TLR2 ligands in a manner that is distinct from the villus epithelium. Intraluminal LPS, a TLR4 ligand, also enhanced microparticle uptake by the FAE and induced DC migration into the FAE, suggesting that other TLRs may modulate FAE functions. We conclude that TLR-mediated signals regulate the gatekeeping functions of the FAE to promote Ag capture by DCs in organized mucosal lymphoid tissues.

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Section: Discussionmentioning

confidence: 99%

TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Chabot

Wagner

Farrant

et al. 2006

The Journal of Immunology

139

116

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“…A s a unique epithelial cell type specializing in Ag sampling, microfold or membranous cells (M cells) are present in the follicle-associated epithelium (FAE) 4 of both GALT and nasopharynx-associated lymphoid tissue, which act as a major inductive site for Ag-specific mucosal immune responses (1,2). Recently, we also identified M cells in the small intestinal villous epithelium, at effector sites far from the FAE, suggesting that Ag sampling via villous M cells may be responsible for induction of systemic Ag-specific immune responses, such as IgG production via the oral route (3).…”

mentioning

confidence: 99%

Comprehensive Gene Expression Profiling of Peyer’s Patch M Cells, Villous M-Like Cells, and Intestinal Epithelial Cells

Terahara

Yoshida

Igarashi

et al. 2008

The Journal of Immunology

163

150

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4 of both GALT and nasopharynx-associated lymphoid tissue, which act as a major inductive site for Ag-specific mucosal immune responses (1, 2). Recently, we also identified M cells in the small intestinal villous epithelium, at effector sites far from the FAE, suggesting that Ag sampling via villous M cells may be responsible for induction of systemic Ag-specific immune responses, such as IgG production via the oral route (3). Still missing, however, were a characterization of the shared and distinctive traits of Peyer's patches (PPs) and villous M cells and a better understanding of the immunological nature of each.Recent comprehensive gene expression analyses using microdissected FAE or whole cells dissociated from the FAE identified genes specifically expressed by PP M cells (4 -6). Similar data, however, have not been available for villous M cells, in part because sufficient numbers of M cells are difficult to isolate from the surrounding intestinal epithelial cells (IECs). In mice, lectin Ulex europaeus agglutinin-1 (UEA-1) possessing affinity for ␣ (1, 2) fucose has been routinely used for the detection of such M cells (3, 7). UEA-1, however, does not alone suffice to identify M cells because it also reacts to goblet cells (3). Our laboratory has recently succeeded in distinguishing M cells from goblet cells by developing a mAb (NKM 16-2-4 mAb) that specifically reacts to murine PP and villous M cells but not goblet cells and IECs (8). Furthermore, our recent separate studies have demonstrated that oral administration of cholera toxin (CT) as mucosal adjuvant resulted in the induction of NKM 16-2-4 mAb ϩ and UEA-1 ϩ M-like cells, which have pocket structure and Ag uptake ability, in the duodenal villous epithelium (Terahara et al., submitted for publication). These recent advances in our understanding of M cells allowed us to define gene expression profiles capable of distinguishing PP M cells, CT-induced villous M-like cells, and IECs. Materials and Methods AnimalsBALB/c mice were purchased from Japan SLC. These mice were maintained under specific pathogen-free conditions in horizontal flow cabinets in our experimental animal facility at the University of Tokyo. Following a previously established protocol (9, 10), CT (List Biologic Laboratories) was dissolved in PBS (20 g/mouse) and then orally administered to BALB/c mice. Two days after CT administration, mice were used for experiments. All animal experiments were approved by the Animal Care and Use Committee of University of Tokyo. Lectins and Abs for the detection of M cellsThe following fluorescence-conjugated lectins and Abs were used for the identification of PP and villous M cells by FACS and histochemistry: PEconjugated UEA-1 (Biogenesis), rhodamine-conjugated UEA-1 (Vector

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“…Treatment of epithelial cells at the basolateral side with C-Cpe (the non-toxic C terminus of Cpe) causes a decrease in TER and increase in paracellular permeability, concomitant with Cldn-4 endocytosis and degradation (2,4). Immunofluorescence staining, Western blotting, and gene expression analysis demonstrate that Cldn-4 is highly expressed in colon, nasopharynx surface epithelia cells as well as on M-cells in Peyer's patch (5,6,7). Reports also show that Cldn-4 can be overexpressed in a variety of cancers including breast, prostate, and colorectal, suggesting a potential for therapies through Cldn-4 targeting (8).…”

mentioning

confidence: 99%

Structural Constraints for the Binding of Short Peptides to Claudin-4 Revealed by Surface Plasmon Resonance

Ling

Liao

Clark

et al. 2008

Journal of Biological Chemistry

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Peptidoglycan recognition protein expression in mouse Peyer’s Patch follicle associated epithelium suggests functional specialization

Cited by 68 publications

References 40 publications

TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Comprehensive Gene Expression Profiling of Peyer’s Patch M Cells, Villous M-Like Cells, and Intestinal Epithelial Cells

Structural Constraints for the Binding of Short Peptides to Claudin-4 Revealed by Surface Plasmon Resonance

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