Mucosal Immunology and Antigen Transport Mechanisms

The mucosal immune system serves as the principal line of defence at interfaces with the external environment, notably in the gastrointestinal, respiratory and urogenital tracts. Its architecture balances selective permeability to nutrients and commensals with robust surveillance against pathogens. A specialised epithelium, often studded with microfold (M) cells, mediates sampling of luminal antigens via transcytosis into underlying lymphoid structures such as Peyer’s patches. There, antigen‐presenting cells including dendritic cells and macrophages process and present antigen to T and B lymphocytes, driving either tolerance or active immunity. Secretory immunoglobulin A (SIgA) emerges as a key effector, neutralising pathogens without provoking inflammation. Cytokine networks and epithelial signalling pathways, including non‐canonical NFκB cascades, finely tune the differentiation and function of M cells and other mucosal constituents, ensuring homeostasis while mounting rapid responses to infection or dysbiosis.

Research from Nature Portfolio

Recent work has revealed that a pancreas–gut axis involving secreted glycoprotein 2 (GP2) plays a crucial protective role during intestinal inflammation. Upregulation of luminal GP2 in response to inflammatory cues binds adhesive commensals, limiting epithelial invasion and mitigating disease severity. In models lacking pancreatic GP2, epithelial barrier disruption and microbial translocation are exacerbated, underscoring a first‐line defence mechanism that complements mucosal antibody responses.

Complementary studies have identified osteoprotegerin (OPG) as a self‐regulator of M cell differentiation. By acting as a soluble decoy receptor for RANKL, OPG restricts excessive M cell formation, balancing antigen surveillance against the risk of pathogen entry. Mice deficient in OPG exhibit increased M cell density, enhanced commensal‐specific immunoglobulin production and improved outcomes in colitis, but also greater susceptibility to invasive pathogens, highlighting the need for tight regulation of antigen transport gateways.

Mucosal Immunology and Antigen Transport Mechanisms publication trend

The graph below shows the total number of articles in mucosal immunology and antigen transport mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Microfold (M) cells: Specialized epithelial cells overlying lymphoid follicles that translocate luminal antigens to immune cells beneath.

Transcytosis: The process by which cells transport macromolecules from one side of an epithelial barrier to the other in vesicles.

Secretory immunoglobulin A (SIgA): A dimeric antibody form prevalent at mucosal surfaces, neutralising pathogens without triggering inflammation.

Follicle‐associated epithelium (FAE): The specialised epithelial layer covering mucosa‐associated lymphoid tissues such as Peyer’s patches.

Peyer’s patches: Aggregates of lymphoid follicles in the small intestine that serve as induction sites for mucosal immune responses.

Dendritic cells: Antigen‐presenting cells that sample antigens, migrate to lymphoid tissues and activate naive T cells.

References

1. Glycoprotein 2 as a gut gate keeper for mucosal equilibrium between inflammation and immunity. Seminars in Immunopathology (2024).
2. C5aR+ dendritic cells fine-tune the Peyer’s patch microenvironment to induce antigen-specific CD8+ T cells. npj Vaccines (2023).
3. M Cells: Intelligent Engineering of Mucosal Immune Surveillance. Frontiers in Immunology (2019).
4. Peyer′s Patches: The Immune Sensors of the Intestine. International Journal of Inflammation (2010).
5. The Peyer’s Patch Mononuclear Phagocyte System at Steady State and during Infection. Frontiers in Immunology (2017).
6. Intestinal non-canonical NFκB signaling shapes the local and systemic immune response. Nature Communications (2019).
7. Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation. Nature Communications (2021).
8. Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity. Nature Communications (2020).