Fighting infections with self-made antibodies

New research reveals the skin’s role as an immune powerhouse, independently producing antibodies to balance its microbiota and prevent harmful infections.

Research: Skin autonomous antibody production regulates host-microbiota interactions. Image Credit: banjongseal324SS / Shutterstock

In a recent study published in the journal Nature, a research team consisting of scientists from the National Institutes of Health and Stanford University investigated how the skin independently produces antibodies to regulate interactions with its microbiota. They explored the skin’s role as an immune organ, uncovering its ability to form specialized immune structures, known as tertiary lymphoid organs, that generate specific antibodies to maintain microbial balance and prevent systemic infections.

Background

The human body coexists with a diverse microbial community, especially at barrier sites such as the skin. Under normal conditions, these microbes influence immune regulation and tissue repair without causing inflammation. The skin microbiota, consisting of commensal organisms like Staphylococcus epidermidis, plays a crucial role in balancing immune responses to prevent harmful overgrowth or infections. Immune responses tailored to microbiota are critical, particularly for barrier tissues such as the skin, which hosts a rich microbial ecosystem.

Immunodeficiencies affecting antibody production are known to increase susceptibility to skin infections, further emphasizing the protective role of antibodies. Recent studies have shown that the skin harbors B cells capable of producing antibodies, challenging prior assumptions that immune responses occur only in lymphoid organs.

However, although serum antibodies are known to react to skin microbes and immunoglobulin coatings are detected on these microorganisms, the mechanisms underlying these responses and their physiological roles remain unclear. This study addresses a key question: how does the skin autonomously mediate microbial interactions under non-inflammatory conditions? Understanding this process is crucial for revealing the skin’s contributions to health and immunity, particularly in regulating microbiota without inflammatory triggers.

About the study

The study utilized murine models to investigate the skin’s ability to produce antibodies independent of secondary lymphoid organs. The researchers colonized the skin with the commensal bacterium Staphylococcus epidermidis (strain NIHLM087) and analyzed immune responses over time. They used techniques such as antibody titer measurements through enzyme-linked immunosorbent assays (ELISA), flow cytometry to identify immune cell populations, and confocal microscopy to visualize immune structures.

In one experiment, pathogen-free mice were topically associated with S. epidermidis, and the antibody responses were monitored. The serum samples were then analyzed for the production of specific immunoglobulin G (IgG) subclasses, particularly IgG2b and IgG2c, which were confirmed to be microbe-specific.

Further analyses revealed that tertiary lymphoid organs—distinct structures within the skin resembling classical germinal centers—developed in response to microbial colonization, enabling local antibody production.

To investigate the role of skin-resident immune cells, the researchers depleted Langerhans cells, which are bone marrow-derived immune dendritic cells that reside in the epidermis, using a specialized mouse model. The team also performed ribonucleic acid (RNA) sequencing of skin-resident B cells, uncovering unique transcriptional profiles associated with antibody production.

Additional experiments chemically inhibited lymphocyte trafficking and utilized mice lacking lymphoid organs, confirming the skin’s capacity to generate humoral responses autonomously.

Results

The results showed that the skin autonomously generates antibodies to regulate microbial interactions and prevent systemic infections. Topical colonization with S. epidermidis induced sustained IgG responses, particularly IgG2b and IgG2c, that were produced locally in the skin.

Furthermore, skin-associated immune structures resembling germinal centers, called tertiary lymphoid organs, played a central role in this process. The formation of these structures depended on Langerhans cells, which facilitated antigen presentation and created an environment conducive to antibody production. Moreover, regulatory T cells in the skin exhibited plasticity, converting into T follicular helper cells to support antibody responses.

The research also demonstrated that skin-resident antibodies controlled microbial colonization and protected against systemic infections. Mice deficient in secondary lymphoid organs or lymphocyte trafficking maintained localized IgG responses, indicating that the skin operates as an independent immune compartment.

B-cell profiling revealed unique transcriptional signatures, including evidence of somatic hypermutations, supporting ongoing local immune activity. The genetic and chemical interventions confirmed that IgG2b and IgG2c production relied on skin-specific mechanisms rather than classical lymphoid structures.

Conclusions

To conclude, the study highlighted the skin’s remarkable ability to function as an autonomous immune organ. By forming tertiary lymphoid structures, the skin was found to generate localized antibodies that maintain microbial balance and provide infection resistance.

These findings redefine our understanding of barrier immunity, highlighting the skin’s active role beyond its physical barrier function. This research advances the concept of immune compartmentalization and offers insights into targeted therapies for infections and microbiota-related disorders. The discovery of skin-specific humoral immunity may also have implications for understanding chronic skin conditions and developing novel vaccine strategies.