Peyer’s Patch Insights: Location, Structure, and Function

Peyer’s patches play a crucial role in immune surveillance within the intestines, detecting and responding to pathogens while maintaining tolerance to beneficial microbes. Given the gastrointestinal tract’s constant exposure to foreign antigens, these lymphoid structures are vital for gut immunity.

Location And Structural Features

Peyer’s patches are concentrated in the ileum, the final segment of the small intestine, where microbial density is highest. Unlike diffusely distributed lymphoid tissues, they form organized clusters within the intestinal wall, embedded in the mucosa and extending into the submucosa. Their number varies, typically ranging from 30 to 40 patches in humans, depending on age and physiology.

Unlike encapsulated lymphoid organs like lymph nodes, Peyer’s patches lack a fibrous capsule, integrating seamlessly into the intestinal lining. They appear as dome-shaped aggregates of lymphoid follicles, each containing a germinal center for B cell proliferation and a surrounding mantle zone with a mix of immune cells. The overlying follicle-associated epithelium (FAE) is specialized for antigen sampling, featuring fewer goblet cells and reduced mucus production to enhance interaction with intestinal contents.

Beneath the FAE, the subepithelial dome (SED) acts as a transition zone, densely populated with antigen-presenting cells. This region processes material transported through the epithelium. High endothelial venules (HEVs) within the tissue facilitate the selective migration of circulating lymphocytes, maintaining the dynamic immune environment of Peyer’s patches.

Lymphoid Organization

Peyer’s patches are structured to efficiently process antigens entering the intestine. Their lymphoid follicles, the primary sites for immune cell aggregation and maturation, contain germinal centers where B cells undergo somatic hypermutation to refine antigen recognition. The surrounding mantle zone houses naïve and memory B cells, contributing to long-term immunity.

Fibroblastic reticular cells (FRCs) form a scaffold around these follicles, guiding lymphocyte movement and maintaining structural integrity. HEVs, interspersed throughout, express adhesion molecules that enable lymphocytes to exit the bloodstream and home to Peyer’s patches.

The FAE, which forms the interface between the intestinal lumen and underlying immune structures, is thinner than typical intestinal epithelium, with fewer goblet cells. Embedded within it, microfold (M) cells transport antigens to immune cells in the SED. These specialized cells lack microvilli and form pocket-like structures to facilitate antigen uptake.

Immunological Roles

Peyer’s patches function as immune surveillance hubs, identifying harmful pathogens while maintaining tolerance to dietary components and gut microbes. They achieve this balance through antigen sampling, immune cell activation, and the production of regulatory and effector molecules.

Upon antigen entry, B cells in the germinal centers undergo class-switch recombination, producing immunoglobulin A (IgA), a mucosal antibody that neutralizes pathogens without triggering excessive inflammation. Secretory IgA prevents bacterial adherence to the intestinal lining, preserving gut homeostasis.

Peyer’s patches also prime antigen-specific T cells, which migrate to distant mucosal sites for immune defense. Regulatory T cells (Tregs) within these structures promote immune tolerance, preventing unnecessary activation. Local cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) help shape immune responses that favor tolerance over inflammation.

Cell Types Involved

Peyer’s patches contain diverse immune cell populations, each playing a specialized role in maintaining immune function.

B Cells

B cells dominate the germinal centers, proliferating and differentiating into IgA-secreting plasma cells. Unlike systemic B cells, those in Peyer’s patches are primed for mucosal immunity, favoring IgA class switching. This process is driven by interactions with follicular dendritic cells and cytokines like TGF-β.

Within germinal centers, B cells undergo somatic hypermutation to enhance antigen affinity. High-affinity B cells then migrate to the lamina propria, where they differentiate into long-lived plasma cells that continuously secrete IgA into the intestinal lumen, supporting mucosal defense.

T Cells

T cells, primarily located in interfollicular regions and the SED, include CD4+ helper T cells and CD8+ cytotoxic T cells. CD4+ T cells aid B cells in antibody class switching and affinity maturation through direct contact and cytokine signaling, particularly via interleukin-21 (IL-21).

Regulatory T cells (Tregs) help maintain immune tolerance to dietary antigens and commensal bacteria. These cells, expressing the transcription factor FoxP3, secrete immunosuppressive cytokines like IL-10 to prevent excessive immune activation.

M Cells

Microfold (M) cells, embedded in the FAE, lack a thick glycocalyx and microvilli, facilitating direct interaction with luminal antigens. Their primary role is to transport antigens, including bacteria and viruses, from the intestinal lumen to immune cells in the SED.

Through transcytosis, M cells internalize antigens via endocytosis or phagocytosis and deliver them to antigen-presenting cells such as dendritic cells and macrophages. These cells then process and present antigens, initiating immune responses. M cells also express glycoprotein 2 (GP2), enhancing their ability to bind and transport specific bacterial components.

Relationship With Gut Microbes

Peyer’s patches interact closely with gut microbiota, shaping immune responses while maintaining a balance between defense and tolerance. Microbial exposure influences their development and function, as germ-free animals exhibit underdeveloped Peyer’s patches with fewer immune cells.

Commensal bacteria stimulate IgA production, regulating microbial composition and preventing harmful species’ overgrowth. Peyer’s patches actively sample microbial components to distinguish between pathogenic and symbiotic organisms. Antigen-presenting cells process bacterial antigens, promoting immune tolerance to beneficial microbes while triggering defensive responses against pathogens. This selective recognition is mediated by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs).

Dysregulation in this process can contribute to inflammatory disorders like Crohn’s disease, where an exaggerated immune response to gut bacteria leads to chronic inflammation. By mediating host-microbe interactions, Peyer’s patches help maintain gut homeostasis.

Associated Inflammatory Responses

When immune tolerance mechanisms fail, Peyer’s patches can become sites of excessive immune activation, contributing to inflammatory conditions like inflammatory bowel diseases (IBD). In Crohn’s disease and ulcerative colitis, these lymphoid structures show increased immune cell infiltration and heightened cytokine production. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) contribute to tissue damage and intestinal barrier disruption.

Pathogens like Salmonella and Yersinia exploit M cells to enter Peyer’s patches, evading immune detection and establishing infection. In response, these structures recruit neutrophils and macrophages, triggering localized inflammation. While necessary for pathogen clearance, excessive activation can cause tissue damage and increased intestinal permeability. Understanding these inflammatory pathways offers insights into therapeutic strategies for gut-related diseases.