Our study shows that AhR activation by FICZ reduces FcεRI and upregulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD.

Antibody-based immunotherapy of leukemia requires the targeting of specific antigens on the surface of blasts. The Fc gamma receptor (CD64) has been investigated in detail, and CD64-targeting immunotherapy has shown promising efficacy in the targeted ablation of acute myeloid leukemia (AML), acute myelomonocytic leukemia (AMML) and chronic myeloid leukemia cells (CML). Here we investigate for the first time the potential of FcaRI (CD89) as a new target antigen expressed by different myeloid leukemic cell populations. For specific targeting and killing, we generated a recombinant fusion protein comprising an anti-human CD89 single-chain Fragment variable and the well-characterized truncated version of the potent Pseudomonas aeruginosa exotoxin A (ETA'). Our novel therapeutic approach achieved in vitro EC 50 values in range 0.2-3 nM depending on the applied stimuli, that is, interferon gamma or tumor necrosis factor alpha. We also observed a dose-dependent apoptosis-mediated cytotoxicity, which resulted in the elimination of up to 90% of the target cells within 72 hr. These findings were also confirmed ex vivo using leukemic primary cells from peripheral blood samples of three previously untreated patients. We conclude that CD89-specific targeting of leukemia cell lines can be achieved in vitro and that the efficient elimination of leukemic primary cells supports the potential of CD89-ETA' as a potent, novel immunotherapeutic agent.Under normal physiological conditions, the Fc-alpha receptor (FcaR, CD89) is present on monocytes, macrophages, neutrophils and eosinophils. Its biological function is to interact with IgA-opsonized targets, triggering several immunological defense processes, e.g. phagocytosis, antibody-dependent cellmediated cytotoxicity and the stimulation of inflammatory mediators. 1 In many human tissues, most of the CD89 1 cells are neutrophils and monocytes/macrophages. Furthermore, although monocytes in the blood express relatively high levels of CD89, most tissue macrophages (particularly those located in the gut lamina propria) tend not to express CD89 on the surface, with a parallel downregulation of CD14. 2 This suggests that the abundance of CD89 depends on the differentiation stage of myeloid cells. The biological relevance of CD89 downregulation during the maturation of myeloid precursor cells is unknown.On the other hand, the presence of anomalous numbers of myeloid cells in the blood is indicative of several myelogenous hematological malignancies, with AML and CML being the most common. 3 The different forms of myeloid leukemia have been categorized using the French-American-British (FAB) system divided into eight subtypes (M0-M7). The World Health Organisation (WHO) uses expanded criteria. 4 A standard panel of markers is used for detailed diagnosis and classification, including Fc gamma receptor (FcgRI) (CD64) which is present on AML subtypes M0-M5 in varying degrees. 5 Thus far, there is no evidence that other Fc receptors can be used as diagnostic antigens or therapeutic targets in A...

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Acne vulgaris is a very common skin diseases associated with significant social, psychological, and economic burden and is the second highest cause of lost DALYs among skin diseases. Treatments for acne are imperfect and far from curative, in part as our understanding of disease pathogenesis is far from complete. Nonetheless, acne research is chronically underfunded. As of 2015, acne received just a half a percent of total funding in dermatology, less funding than diseases that represent a much smaller global burden, such as leprosy, fungal skin diseases, and alopecia. With big data analytics available through Google Trends, we see that internet searches for acne vulgaris have nearly doubled worldwide since 2004 with peaks in January and August each year. These searches far exceed those for other skin conditions such as skin cancer, psoriasis, and eczema. As of 2017, top trending acne-related searches focused on both medical and homeopathic remedies for the disease. Despite public interest high and on the rise, acne-related research funding by the National Institutes of Health has been in sharp decline, now at $1.8 million, just 26% of its total in 2008. Despite this overall drop, the areas of acne research that have experienced some growth include skin microbiome, bacteriophages, and sebum and hair follicle regulation. Funding for acne clinical outcomes through Acne Core Outcomes Research Network (ACORN) has remained relatively stable. Immunology research into acne has suffered the most; funding as a group has dropped from $3.7 million to $0. With interest in acne on the rise and funding opposing this trend, it is important to reassess where our understanding of this disease currently stands, and where we anticipate trends in research to go, which may influence the way we approach acne going forward.