Conclusion: This study's findings regarding adjuvant-dependent GC responses and IgG glycosylation programming may aid in the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns in the GC.

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Pro- and anti-inflammatory effector functions of IgG antibodies (Abs) depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0) IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE) patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors), administered in high doses (2 g/kg) to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR) transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II)-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

Atopic dermatitis (AD) is a common and multifactorial skin disease. Genetically determined skin barrier defects and a dysregulated immune system lead to chronic inflammation. It is known that atopic and healthy skin differ in bacterial colonization. Atopic skin is associated with a lower microbiota diversity and higher amounts of potentially pathogenic bacteria like Staphylococcus aureus. However, it is still subject of debate whether this different microbiota composition is mainly a result or a cause of the inflammatory state in AD. To investigate this question further, we started to analyze the influence of the skin microbiota of healthy individuals and AD patients on a 3D skin equivalent representing healthy skin. To this end, defined skin areas were rinsed with a saline/detergent solution to harvest the microbiota. Subsequently, the rinsing solution was sequentially centrifuged and stored at-80 C in a glycerol-pellet. These microbiota samples were then applied to the surface of a 3D skin equivalent. After stimulation, gene expression of inflammatory mediators, barrier and defense molecules was analyzed by real-time PCR. The microbiota of AD patients was compared with localization-, gender-and age-matched microbiota samples of healthy control persons. As a general result, we observed that the microbiota-treatment of the 3D skin equivalents induced the expression of several inflammatory and defense mediators (e.g. cytokines, antimicrobial peptides). The microbiota derived from lesional AD-skin induced higher levels of several inflammatory mediators as compared to the microbiota of healthy skin or non-lesional AD skin. Especially the expression of the AD-associated inflammatory mediator thymic stromal lymphopoietin (TSLP) was markedly increased by the microbiota derived from lesional AD skin. These findings indicate that the altered skin microbiota in AD may amplify the inflammation process through the induction of host inflammatory mediators such as TSLP.

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