Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutaneous procedure may lead to new strategies in prevention of type 1 diabetes in humans

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008

BACKGROUND: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. METHODS: Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. RESULTS: Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. CONCLUSIONS: The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series